| 1. |
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| 2. |
- Amin, Kawa, 1963-
(författare)
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The Role of the T lymphocytes and Remodeling in Asthma.
- 2016
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 39:4, s. 1475-1482
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Tidskriftsartikel (refereegranskat)abstract
- In allergic asthma (AA), inflammatory changes in the airway epithelium may contribute to the characteristic pathophysiology and symptoms. The presence of T lymphocytes, eosinophils, mast cells and macrophages, the presence of cytokines, and also structural changes in the airway mucous membrane are characteristic for asthma. Bronchial biopsy specimens were obtained from 33 AA, 25 nonallergic asthma (NAA), and 20 healthy controls (HC). This study used immunohistochemical techniques for identified monoclonal antibodies (CD3, CD4, CD8, CD25, ECP, MBP, tenascin, and laminin) in the bronchi. The highest number of eosinophils and T lymphocyte cells in bronchial biopsies was found in AA, and NAA. The number of T lymphocytes in AA was significantly higher than in NAA and HC. The degree of epithelial damage was higher in the AA group compared to the other groups. The tenascin- and laminin-positive layers in AA were thicker than other groups. In AA, a significant negative correlation was found between epithelial integrity and the count for eosinophils or T lymphocytes. T lymphocytes and eosinophils in AA were found in the area of epithelial and lamina propria damage. This article suggests that T lymphocytes may not only contribute to the chronic airway inflammatory response, airway remodeling, and symptomatology but may also have a central role at the initiation of the allergic immune response. Th-targeted therapy would be of considerable interest in controlling AA. Having more knowledge on the roles of T lymphocytes in the pathogenesis of allergic inflammation highlights the contributions of these cells in regulating and may lead to a new therapeutic target-AA.
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| 3. |
- Bjersing, Jan, 1966, et al.
(författare)
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Impact of site-specific nucleobase deletions on the arthritogenicity of DNA
- 2004
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Ingår i: Inflammation. - 0360-3997. ; 28:3, s. 159-68
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Tidskriftsartikel (refereegranskat)abstract
- Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG ODN) potently stimulate the innate and acquired immune system. We have compared the in vivo and in vitro inflammatogenic properties of CpG ODNs containing a specific nucleobase deletion either 5'-upstream (ODN-2) or 3'-downstream (ODN-3) of the CpG motif, comparing with a prototype CpG ODN (ODN-1). The frequency of arthritis was similar after intra-articular (i.a.) injections of ODN-1 or ODN-3, but was significantly lower (p < 0.02) after i.a. injections of ODN-2. In vitro production of the pro-inflammatory cytokine TNF-alpha was higher in mouse spleen cell cultures exposed to ODN-2 in comparison to ODN-1. In addition, the level of IL-10 induced by ODN-2 was higher than that induced by ODN-1. On the other hand, TNF-alpha, IL-10, and MCP-1 levels, as well as splenocyte proliferative responses were all significantly lower for ODN-3 than for ODN-1. These results suggest that a 5'-upstream nucleobase deletion reduces arthritogenicity, while maintaining or increasing the production of pro- and anti-inflammatory factors. In contrast, a 3'-downstream nucleobase deletion has no effect on arthritogenicity, despite significantly lower levels of proliferation and pro- and anti-inflammatory cytokines, compared with ODN-1. This study indicates that specific structural elements within the ODN sequence but outside the CpG motif, modulate the immunostimulatory properties of CpG ODNs.
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| 4. |
- Bjersing, Jan, 1966, et al.
(författare)
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The arthritogenic and immunostimulatory properties of phosphorothioate oligodeoxynucleotides rely on synergy between the activities of the nuclease-resistant backbone and CpG motifs
- 2004
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Ingår i: Inflammation. - 0360-3997. ; 28:1, s. 39-51
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Tidskriftsartikel (refereegranskat)abstract
- Experiments with immunostimulatory unmethylated CpG-containing DNA are usually conducted with nuclease-protected phosphorothioate oligodeoxynucleotides (S-ODNs), rather than phosphodiester oligodeoxynucleotides (O-ODNs). We compared the murine immune responses to S-ODNs and O-ODNs that either contained or lacked CpG motifs. Both CpG and non-CpG S-ODNs induced synovitis, as did sequence-matched CpG O-ODN, but not GpC O-ODN. There was a minimum length requirement for arthritogenic S-ODNs since a CpC dinucleotide S-ODN did not induce arthritis. There were both sequence- (CpG > non-CpG) and backbone-dependent (S-ODN > O-ODN) differences in the levels of DNA-induced arthritis upon intra-articular injection with the ODNs. However, CpG O-ODN being an exception, induced more severe arthritis than the GpC S-ODN. The levels of in vitro proliferation and production of IL-6, TNF-alpha, IL-12, and RANTES by splenocytes following exposure to CpG S-ODN were significantly higher than those induced by CpG O-ODN. In addition, both proliferative responses and cytokine production induced by S-ODN-stimulated splenocytes increased significantly when the S-ODN contained a CpG motif. Transcription factor NFkappaB was activated by both CpG S-ODN and CpG O-ODN but interestingly not by GpC S-ODN. This indicates that the NFkappaB signal pathway modulates CpG-mediated immunostimulation, while sequence-independent immune activation by the phosphorothioate backbone is probably signalled via a different pathway.
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| 7. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Fu, Huamei, 1979, et al.
(författare)
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A bactericidal cecropin-A peptide with a stabilized alpha-helical structure possess an increased killing capacity but no proinflammatory activity
- 2004
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 28:6, s. 337-43
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Tidskriftsartikel (refereegranskat)abstract
- Antibacterial peptides are part of the innate immune system in a variety of different species including humans. Some of these peptides have also been shown to have effects on immune competent cells such as professional phagocytes. We have recently shown that a cecropin-like peptide from Helicobacter pylori, Hp(2-20), in addition to being bactericidal possesses proinflammatory effects and can recruit and activate neutrophils as well as monocytes. It is well established that cecropins have the ability to adopt amphipathic alpha-helices, which is thought to be required for their bactericidal activity. In this study we show the same structural requirements for Hp(2-20). Breaking the helical structure of Hp(2-20) reduced the antibacterial effect and abolished its proinflammatory activity. A C-terminal truncated cecropin A peptide that highly resembles Hp(2-20) failed to activate neutrophils and computer-based structural simulations revealed a difference between the two peptides in the stability of their helical structures. A hybrid peptide with amino acid substitutions stabilizing the alpha-helical structure of the truncated cecropin A peptide did not introduce any proinflammatory activity; the bactericidal activity was, however, increased. We thus conclude that the proinflammatory effect of Hp(2-20) is a unique sequence-specific feature of the peptide and the ability to adopt a stable amphipathic helix is a necessary but not sufficient criterion for the functional dualism of the peptide.
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| 13. |
- Gerdin, Bengt, 1947-, et al.
(författare)
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Permeability-increasing ability of PAF-acether in rat skin.
- 1985
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Ingår i: Inflammation. - 0360-3997 .- 1573-2576. ; 9:1, s. 107-12
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-activating factor (PAF-acether), a phospholipid compound with effects on several cells, e.g., platelets and polymorphonuclear leukocytes (PMNs), was examined for its effect on microvascular permeability in rat skin. It was found to increase microvascular permeability, measured as exudation of [125I]human serum albumin, in amounts exceeding 1 pmol, and was more than 1000 times as potent as histamine. The effect was independent of cell infiltration, as no accumulation of PMNs, measured as the amount of myeloperoxidase in the skin, occurred and as the response was unaltered in animals rendered neutropenic due to treatment with an antiserum against PMNs.
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| 14. |
- Gorreja, Frida, et al.
(författare)
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MEFV and NLRP3 Inflammasome Expression Is Attributed to Immature Macrophages and Correlates with Serum Inflammatory Proteins in Crohn ' s Disease Patients
- 2022
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 45, s. 1631-1650
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Tidskriftsartikel (refereegranskat)abstract
- Inflammasomes are intracellular protein complexes whose activation results in proinflammatory cytokines. Inflammasomes are implicated in Crohn ' s disease (CD) pathogenesis, yet the contribution of inflammasomes in intestinal epithelial cells (IECs) versus lamina propria (LP) macrophages is poorly understood. Whether inflammasome expression in intestinal tissue reflects the serum inflammatory protein profile of patients is also not known. We aimed to determine the intestinal cell types where inflammasome expression is increased in CD and if they correlate with the serum protein profile. RT-PCR and NanoString nCounter technology were used to characterize inflammasome gene expression in CD patients and controls. The mucosa, LP and IEC cell fractions and FACS-sorted cells were analyzed. Proximity extension assay with a 92-protein panel was used to determine the serum inflammatory protein profile. Compositional analysis was used to correlate ileum inflammasome gene expression with intestinal mononuclear phagocyte populations. We show that NLRP3 and MEFV inflammasome sensors and downstream effector expression including IL-1 beta are increased in inflamed mucosa of IBD patients and correlate with disease activity. Inflammasome gene expression increased with the abundance of immature intestinal macrophages, and increased IL-1 beta released by CD LP cells correlated with immature macrophage frequency. Inflammasome gene expression was also increased in circulating monocytes, the precursors of immature intestinal macrophages. Finally, the serum inflammatory profile of CD patients correlates with ileal expression of genes related to NLRP3 and MEFV inflammasomes. Overall, we show that MEFV and NLRP3 inflammasome expression in CD intestine is attributed to the accumulation of immature macrophages and correlates with serum inflammatory proteins.
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| 15. |
- Johansson, Sofi, 1975, et al.
(författare)
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CC16 Inhibits the Migration of Eosinophils Towards the Formyl Peptide fMLF but not Towards PGD(2).
- 2009
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 32:2, s. 65-9
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Tidskriftsartikel (refereegranskat)abstract
- Clara cell 16-kDa (CC16) is an anti-inflammatory protein chiefly produced in the lung epithelium. CC16 has been shown to inhibit the migration of rabbit neutrophils and human monocytes toward the formyl peptide N-formyl-methionine-leucin-phenylalanin (fMLF). Eosinophils migrate towards prostaglandin D2 (PGD(2)) and CC16 has been shown to bind to PGD(2). Therefore we investigated if CC16 could inhibit the migration of human eosinophils and neutrophils towards fMLF and/or PGD(2). Migration of eosinophils and neutrophils was assessed in a microplate migration system using specific ligands and receptor antagonists. CC16 inhibited the migration of eosinophils and neutrophils toward fMLF, which is likely to result from the interaction of CC16 with members of the formyl-peptide receptor family. However, CC16 did not inhibit eosinophil migration towards PGD(2). We therefore propose that CC16 may down-modulate the entry of human eosinophils and neutrophils into the airways during inflammation in the lung.
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| 16. |
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| 17. |
- Karawajczyk, Malgorzata, et al.
(författare)
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An Extragranular Compartment of Blood Eosinophils Contains Eosinophil Protein X/Eosinophil-Derived Neurotoxin (EPX/EDN)
- 2013
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 36:2, s. 320-329
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Tidskriftsartikel (refereegranskat)abstract
- Serum and plasma profiles of eosinophil protein X (EPX/EDN) and those of other eosinophil proteins differ in various conditions, suggesting a different mobilisation from storage granules. This work studied the subcellular localisation of EPX/EDN in non-primed and in vivo primed blood eosinophils from healthy and allergic subjects, during and out of the pollen season. Primed eosinophils contain easily mobilisable secretory proteins. By fractionation on sucrose density gradients, EPX/EDN localised in the specific granules as well as in a cytoplasmic extra-granular compartment of low equilibrium density that partially overlapped with vesicular structures, cytosolic proteins and plasma membranes. This compartment was clearly separate from the low density peak of ECP that increases during the pollen season. There were no significant differences in the amounts of EPX/EDN present in the low density peak of healthy and allergic subjects. Immuno-gold labelling electron microscopy showed EPX/EDN in specific granules, cytoplasm and associated to plasma membranes. In conclusion, substantial amounts of EPX/EDN localise in an extra-granular, low equilibrium density compartment of human eosinophils.
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| 18. |
- Karlsson, Anna, 1967, et al.
(författare)
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Secretion of type-1-fimbriae binding proteins from human neutrophil granulocytes.
- 1996
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Ingår i: Inflammation. - 0360-3997. ; 20:4, s. 389-400
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Tidskriftsartikel (refereegranskat)abstract
- Granule matrix proteins secreted from human neutrophils after ionomycin stimulation were separated by SDS-PAGE, blotted onto a polyvinylidene diflouride (PVDF) membrane and overlaid with the mannose-binding lectin concanavalin A (Con A) or Escherichia coli bacteria exposing type-I-fimbriae. Four proteins of approximately 30, 40, 70 and 80 kD, respectively, derived from both the azurophil and the specific granules were shown to expose mannose-containing structures by binding of Con A. Such reactivity was also shown for a 90-kD protein from the light membrane fraction enriched in plasma membrane and secretory vesicles. When blots of granule matrix proteins were exposed to type-I-fimbriated bacteria, a total of seven proteins was recognized; four of the five Con A-binding proteins (40, 70, 80 and 90 kD) was detected also by the bacteria in addition to three proteins not detected by Con A (50, 60 and 100 kD). The role of the secreted type-1-fimbriae binding proteins as anti-adhesin candidates is discussed.
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| 19. |
- Knudsen, J.F., et al.
(författare)
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The cyclooxygenase-2 inhibitor celecoxib is a potent inhibitor of human carbonic anhydrase II
- 2004
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 28:5, s. 285-290
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Tidskriftsartikel (refereegranskat)abstract
- Cyclooxygenase-2 (COX-2) is up-regulated in stromal and inflammatory cells. The inducible COX-2 isoform is expressed during inflammation, in some cancers, and in brain tissue after global and focal ischemia. Tissue acidosis is a dominant factor in inflammation, and contributes to pain and hyperalgesia. Recently, compelling epidemiological and clinical evidence has documented the COX-independent effects of some COX-2 inhibitors (i.e., celecoxib, valdecoxib, and rofecoxib), among these effects are carbonic anhydrase (CA) inhibition. Carbonic anhydrases are zinc metalloenzymes expressed in various cell types, including those of the kidney, where they act as general acid-base catalysts. The kidneys are also known to express the highest concentration of COX-2 messenger ribonucleic acid. Celecoxib, like the prototypic CA inhibitor acetazolamide, is structurally characterized by an unsubstituted sulfonamide moiety. In the present study, we report that celecoxib exhibits the characteristics of a potent CA inhibitor, showing inhibitory human carbonic anhydrase II (hCAII) activity in the nanomolar range. Valdecoxib was relatively less potent. Rofecoxib, which lacks the unsubstituted sulfonamide moiety characteristic of CA inhibitors, showed no significant hCAII inhibitory activity. The current study corroborates our earlier report of structure-activity relationships as predictors of such metabolic events as hyperchloremia, acidosis, and changes in calcium and phosphate disposition, and clinical manifestations associated with CA inhibition reported with celecoxib. These data showing inhibition of hCAII by the unsubstituted sulfonamides celecoxib and valdecoxib, but not by rofecoxib, may have important implications for the elucidation of the mechanisms of action as well as the side effects associated with COX-2 inhibitors. © 2004 Springer Science+Business Media, Inc.
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| 20. |
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| 21. |
- Kämpe, Mary, et al.
(författare)
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PI3-Kinase Regulates Eosinophil and Neutrophil Degranulation in Patients with Allergic Rhinitis and Allergic Asthma Irrespective of Allergen Challenge Model
- 2012
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 35:1, s. 230-239
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Tidskriftsartikel (refereegranskat)abstract
- The PI3K pathway plays a major role in many vital cell processes. Our primary aim was to investigate signalling through PI3K for in vitro degranulation from allergen-primed eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen challenge. Nine patients with allergic rhinitis, eight with allergic asthma and four controls were studied during birch pollen season and after nasal and bronchial allergen challenge. Primed blood eosinophils and neutrophils were stimulated for in vitro degranulation with C3b-coated Sephadex particles, after prior incubation with Wortmannin, a PI3K inhibitor. The released amounts of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) were measured by radioimmunoassay. Wortmannin (10(-6) to 10(-9) M) inhibited ECP, EPO and MPO release in a dose-dependent manner in allergic rhinitis and allergic asthma in all three allergen challenge models. Inhibition of ECP release tended to be lower in the asthmatics in all allergen challenge models, statistically significant compared to the controls during season for 10(-8) M Wortmannin (p = 0.01). A clear propensity towards less inhibition in the rhinitic patients was seen after nasal and bronchial challenge compared to seasonal exposure, significant for ECP (10(-8) M Wortmannin; p = 0.034 and 0.002, respectively). Signalling through PI3K is clearly involved in ECP, EPO and MPO release in allergic rhinitis and allergic asthma irrespective of allergen challenge model. Allergic asthma demonstrated less inhibition of ECP release via PI3K during pollen season, indicating that other pathways play a greater role in eosinophil degranulation in allergic asthma than allergic rhinitis.
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| 22. |
- Larsson, Anders, et al.
(författare)
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Pentraxin 3 Values During Normal Pregnancy
- 2011
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 34:5, s. 448-451
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Tidskriftsartikel (refereegranskat)abstract
- Pentraxin 3 (PTX3) is an inflammatory molecule that has been reported to be a promising early biomarker for subsequent preeclampsia. The levels of PTX3 vary during pregnancy and it is thus a need to establish reference intervals during normal pregnancy. Repeated blood samples were collected from 52 healthy pregnant females. The samples were divided according to collection time into the following groups: week 7-17, week 17-24, week 24-28, week 28-31, week 31-34, week 34-38, before delivery and after delivery. The samples were analyzed for PTX3 with a sandwich ELISA and the 2.5 and 97.5 percentiles for each sample period was calculated. There was a continuous increase of serum PTX3 as pregnancy progressed. The increase was most evident after week 31 with the highest levels just before delivery.
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| 23. |
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| 24. |
- Lima, Rafael R, et al.
(författare)
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Diffuse axonal damage, myelin impairment, astrocytosis and inflammatory response following microinjections of NMDA into the rat striatum
- 2008
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 31:1, s. 24-35
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Tidskriftsartikel (refereegranskat)abstract
- White matter damage and inflammatory response are important secondary outcomes after acute neural disorders. Nevertheless, a few studies addressed the temporal outcomes of these pathological events using non-traumatic models of acute brain injury. In the present study, we describe acute inflammatory response and white matter neuropathology between 1 and 7 days after acute excitotoxic striatal damage. Twenty micrometer sections were stained by hematoxylin and eosin technique for gross histopathological analysis and immunolabed for neutrophils (anti-mbs-1), activated macrophages/microglia (anti-ed1), astrocytes (anti-gfap), damaged axons (anti-beta app) and myelin basic protein (MBP). Recruitment peak of neutrophils and macrophages occurred at 1 and 7 days post-nmda injection, respectively. Diffuse damaged axons (beta-app + end-bulbs) were apparent at 7 days, concomitant with progressive myelin impairment and astrocytosis. Further studies using electron microscopy and blockers of inflammatory response and glutamatergic receptors should be performed to confirm and address the mechanisms of white matter damage following an excitotoxic lesion.
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| 25. |
- Lindbom, John, et al.
(författare)
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Interferon γ-induced gene expression of the novel secretory phospholipase A2 type IID in human monocyte-derived macrophages is inhibited by lipopolysaccharide
- 2005
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 29:2-3, s. 108-117
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Tidskriftsartikel (refereegranskat)abstract
- Phospholipase A2 (PLA2) is a superfamily of enzymes that may play a major role in airways inflammation. We investigated the effect of interferon-γ (IFN-γ) on the gene expression of 19 different PLA2 types in human monocyte-derived macrophages and nasal epithelial cells (RPMI 2650). The cells were stimulated with IFN-γ for different lengths of time (up to 48 h), and the mRNA levels of the different PLA2 types were determined by reverse transcriptase–PCR (RT-PCR) and normalized to those of the house-keeping gene, GAPDH. It appeared that IFN-γ clearly increased the expression of secretory PLA2 IID (but not IIA) in macrophages, while both PLA2 IID and IIA were upregulated in RPMI 2650 cells. Moreover, after 18 h, the mRNA levels of cytosolic PLA2 IVA were 2–3 times higher in IFN-γ-stimulated macrophages than controls, while there was no such effect of IFN-γ in RPMI 2650 cells. Lipopolysaccharide (LPS) augmented the increased gene expression of PLA2 IVA but decreased both the basal and the IFN-γ-induced PLA2 IID mRNA expression in macrophages (but not in RPMI 2650 cells). The NF-κB inhibitor Pyrrolidine dithiocarbamate (PDTC) and the phoshatidylinositol 3-kinase (PI3K) inhibitor wortmannin were employed to get an insight into the mechanism behind these observations. Incubation of macrophages with PDTC had no effect on the LPS impairment of PLA2 IID gene expression, but inhibited the LPS mediated activation of PLA2 IVA. No significant effect was noted of PDTC on IFN-γ stimulation, while PI3K had no effect at all on any of the stimuli used. Furthermore, LPS (but not IFN-γ) increased the mRNA levels of the nuclear factor (NF)-κB inhibitors α and ξ in macrophages, but not in RPMI 2650 cells. These findings indicate that (a) the gene expression of secretory types PLA2 IID and IIA in response to IFN-γ is much dependent on cell type, and (b) the regulation of PLA2 type IID in human macrophages is clearly different from that of PLA2 type IVA. (c) PLA2 IVA is probably under control of both NF-κB and IFN-γ-responsive elements (GRE) or IFN-γ-activating sites (GAS). The possibility that PLA2 IID is involved in cytokine-mediated inflammation in the nasal mucosa is inferred, as is the potential role of PLA2 IID in the host defense against LPS-containing bacteria.
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| 26. |
- Lingblom, Christine, 1984, et al.
(författare)
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Topical Corticosteroids Do Not Revert the Activated Phenotype of Eosinophils in Eosinophilic Esophagitis but Decrease Surface Levels of CD18 Resulting in Diminished Adherence to ICAM-1, ICAM-2, and Endothelial Cells.
- 2014
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 1573-2576 .- 0360-3997. ; 37:6, s. 1932-1944
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Tidskriftsartikel (refereegranskat)abstract
- Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.
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| 27. |
- Ljunghusen, O, et al.
(författare)
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Endotoxemia and complement activation after severe burn injuries--effects on leukocytes, soluble selectins, and inflammatory cytokines.
- 1996
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Ingår i: Inflammation. - 0360-3997 .- 1573-2576. ; 20, s. 229-
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Tidskriftsartikel (refereegranskat)abstract
- In this study we followed the development of an inflammatory response in a group of patients the first week after a burn injury. We detected elevated plasma endotoxin levels, on at least one occasion, in 6 of 8 patients. No endotoxin was detected in the two patients with the lowest total burned surface area (< or = 30%). We found evidence of complement activation as increased C3a levels, in parallel with a production of inflammatory cytokines (TNF-alpha, IL-6). The TNF-alpha levels increased significantly during the observation period, while the IL-6 levels were elevated already at admission, and remained so. Elevated levels of soluble E-selectin were detected, indicating endothelial cell activation. Despite the inflammatory response and a loss of inflammatory cells during the first days of the monitoring period, we found no evidence of cellular activation measured as increased expression of beta 2 integrin CD11b, nor increased plasma levels of soluble L-selectin.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Magnusson, Maria K, 1972, et al.
(författare)
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The Anti-inflammatory Immune Regulation Induced by Butyrate Is Impaired in Inflamed Intestinal Mucosa from Patients with Ulcerative Colitis.
- 2020
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 1573-2576 .- 0360-3997. ; 43, s. 507-517
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Tidskriftsartikel (refereegranskat)abstract
- Altered gut microbiota composition and reduced levels of short-chain fatty acids, such as butyrate, have been identified as key components of ulcerative colitis (UC). We aimed to determine and compare effects of butyrate on the intestinal immune profile of UC patients with active disease and non-inflamed controls. Biopsies were cultivated during 6 h with or without butyrate. Cytokines were measured in supernatants and mRNA gene expression was analyzed in biopsies using Qiagen RT2 Profiler PCR Arrays. The intestinal immune profile of cultured biopsies, as determined by mRNA gene expression and secreted cytokines, differed between inflamed UC samples and controls. Principal component analysis revealed that addition of butyrate differently regulated mRNA expression in inflamed biopsies from UC and non-inflamed biopsies from controls. Highly discriminant and predictive orthogonal partial least squares discriminant analyses identified 29 genes for UC (R2 = 0.94, Q2 = 0.86) and 23 genes for controls (R2 = 0.90, Q2 = 0.71) that were most regulated by butyrate. UC displayed more up-regulation of genes as compared with controls, and controls displayed the most prominent down-regulations. Ingenuity Pathway Analysis identified a down regulation of the Neuroinflammation Signaling pathway and predicted inhibition of the categories Inflammatory response, cellular movement, and cellular development as top diseases and functions, respectively, for controls but not for UC. In conclusion, butyrate has a different effect on gene regulation and more potently down-regulates gene expression of inflammatory pathways in non-inflamed controls than in inflamed tissue of UC patients. These discrepancies may at least partly explain why anticipated anti-inflammatory effects of local butyrate induction or supplementation are not always obtained.
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| 32. |
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| 33. |
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| 34. |
- Nannmark, Ulf, 1958, et al.
(författare)
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Indomethacin, (-)-terbutaline (beta 2 agonist), and (+)-terbutaline in acute inflammation induced by repeated ischemia in hamster cheek pouch.
- 1985
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 9:2, s. 173-81
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Tidskriftsartikel (refereegranskat)abstract
- A mild and controlled acute inflammatory reaction in hamster cheek pouch was created without any exogenous, but rather by locally activated and liberated, mediators. A pressure of 60 mm Hg was applied to part of the everted cheek pouch eight times with a 10-min recovery period in between. The microvascular response was followed by intravital microscopy and the permeability changes were monitored with intravital fluoroscopy and intravenous FITC dextran (mol wt 150,000). The number of extravasated polymorphonuclear leukocytes (PMNLs) was calculated by a new, whole tissue, histological technique. In three experimental groups (-)-terbutaline (beta 2-receptor agonist) 0.05 mg/100 g body wt., (+)-terbutaline 0.05 mg/100 g body wt., and indomethacin 2 mg/100 g body wt. was given intravenously before pressure was applied. A fourth group, with no drug given, served as control. There was a rapid increase in the number of FITC dextran leakages and extravasated PMNLs in the control group. Indomethacin almost completely inhibited FITC dextran permeability and extravasation of PMNLs. The beta 2 agonist markedly diminished the number of FITC dextran leakages for 75 min. The number of extravasated PMNLs was also reduced. Treatment with (+)-terbutaline, which is supposed to have no beta 2-receptor effect, gave a slight reduction in number of FITC dextran leakages and almost a complete inhibition of PMNL extravasation. Thus we conclude that indomethacin is a very potent antiinflammatory agent even in the early phase of inflammation. (-)-Terbutaline diminished the inflammatory response, probably by preventing endothelial gap formation. (+)-Terbutaline prevented PMNL extravasation either by interaction with the PMNL itself or with the endothelium.
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| 35. |
- Nilsson, Lennart, et al.
(författare)
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Effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases in hypercholesterolemic individuals.
- 2011
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Ingår i: Inflammation. - : Springer-Verlag New York. - 0360-3997 .- 1573-2576. ; 34:4, s. 225-230
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Tidskriftsartikel (refereegranskat)abstract
- Statins are potent lipid-lowering drugs but anti-inflammatory effects have also been suggested. Our aim was to investigate the effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases (MMPs). Eighty hypercholesterolemic men were randomized to simvastatin 40 mg or placebo for 6 weeks. Simvastatin treatment significantly reduced C-reactive protein (CRP) levels while interleukin (IL)-6 levels remained unchanged. The ex vivo release of IL-1beta and IL-6 was not altered by simvastatin, whereas the release of TNF-alpha and IL-8 increased after 6 weeks of simvastatin treatment. Similarly, the circulating levels of MMP-3 and TIMP-1 remained unaffected by simvastatin while MMP-9 increased. However, none of the effects except for the CRP reduction within the simvastatin group reached statistical significance when compared to the placebo group. Our findings are in contrast to previous in vitro and animal data and question the in vivo relevance of some of the pleiotropic effects of simvastatin.
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| 36. |
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| 37. |
- Nyhlén, Kristina, 1967-, et al.
(författare)
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Modulation of Cytokine-Induced Production of IL-8 in Vitro by Interferons and Glucocorticosteroids
- 2004
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Ingår i: Inflammation. - 0360-3997 .- 1573-2576. ; 28:2, s. 77-88
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-8 (IL-8) has been implicated in the pathogenesis of inflammation and cancer. Intracellular levels of cytokine-induced IL-8 in human umbilical vein endothelial cells (HUVEC) were modulated using interferons and steroids to further elucidate their mechanism. Basal and cytokine-induced production of IL-8 was studied using a novel ELISA application, flow cytometry, and RT-PCR. The intracellular amount of IL-8 increased after 6-h stimulation with TNF- (30%) or IL-1ß (55%) which was doubled when Golgi transport was disrupted using monensin. IFN-γ decreased the intracellular amount of IL-8 by 60% in both unstimulated and TNF--stimulated cells, but only when secretion was blocked using monensin. Dexamethasone inhibited the TNF--induced production by 33%, but had no effect in unstimulated cells. Our study indicated that both, dexamethasone and IFN inhibit TNF--induced upregulation of IL-8 at the mRNA level. It could be speculated that they inhibit IL-8 production by affecting different gene regulatory mechanisms.
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| 38. |
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| 39. |
- Pettersson, Mattias, Ph.D. 1972-, et al.
(författare)
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Ti Ions Induce IL-1β Release by Activation of the NLRP3 Inflammasome in a Human Macrophage Cell Line
- 2022
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Ingår i: Inflammation. - : Springer. - 0360-3997 .- 1573-2576. ; 45, s. 2027-2037
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate whether titanium (Ti)-induced release of interleukin (IL)-1β acts through the assembly of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome. In addition, we examined whether particulate Ti or TiO2 activates the same intracellular pathways with the assembly of the NLRP3 inflammasome as Ti ions. Ti ions are known to induce IL-1β maturation and release by the formation of metal-protein aggregates. Wild-type THP-1 (wt.) cells and NLRP3- and ASC- (apoptosis-associated speck-like protein containing caspase recruitment domain (CARD)) knockdown cells were used in the experimental analyses. Macro- and nanoparticles (NPs) of both Ti and TiO2 were used as test agents. IL-1β release as a biomarker for inflammasome activation and cell viability was also analyzed. Periodate-oxidized adenosine triphosphate (oATP) was used to attenuate downstream signaling in NLRP3 inflammasome activation. Cellular uptake of Ti was examined using transmission electron microscopy. Cells exposed to the Ti-ion solution showed a dose-dependent increase in the release of IL-1β; conversely, exposure to particulate Ti did not result in increased IL-1β release. Cell viability was not affected by particulate Ti. Knockdown cells exposed to Ti showed a statistically significant reduction in the release of IL-1β compared with wt. cells (p < 0.001). Cellular uptake was detected in all Ti mixtures, and aggregates with various structures were observed. Ti ion-induced release of bioactive IL-1β in THP-1 cells involves the assembly of the NLRP3 inflammasome.
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| 40. |
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| 41. |
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| 42. |
- Sennerby, Lars, 1960, et al.
(författare)
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Activation and migration of leukocytes and vascular leakage induced by serum-opsonized zymosan particles in hamster cheek pouch.
- 1989
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 13:1, s. 91-102
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Tidskriftsartikel (refereegranskat)abstract
- The effect of topically applied serum-opsonized zymosan (SOZ) and zymosan-activated serum (ZAS) was studied in the hamster cheek pouch. Our data suggest that early vascular leakage, evaluated by intravital fluorescence microscopy after injection of FITC-dextran, and accumulation of polymorphonuclear granulocytes (PMNGs), quantitated in fixed whole tissue specimens, induced by ZAS and SOZ were caused by complement activation, whereas the late leakages (greater than 20 min after SOZ application) was PMNG-dependent. Inhibition of prostaglandin and leukotriene synthesis by indomethacin, nordihydroguaiaretic acid (NDGA), and BW755C influence early and late vascular leakage as well as accumulation of PMNGs. These drugs also inhibited the activation of hamster PMNGs in vitro, as evaluated by chemiluminescence, in a dose-dependent manner. (-)-Terbutaline, an adrenergic beta agonist, decreased vascular leakage but had no effect on PMNG activation and accumulation.
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| 43. |
- Shareef, Suhayla, et al.
(författare)
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The Association between β-dystroglycan in Airway Smooth Muscle and Eosinophils in Allergic Asthma : β-dystroglycan in Airway Smooth Muscle and Eosinophils in Allergic Asthma
- 2021
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Ingår i: Inflammation. - Switzerland AG : Springer Nature. - 0360-3997 .- 1573-2576. ; 44:3, s. 1060-1068
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic asthma (AA) is a complex disorder with heterogeneous features of airway hyperresponsiveness, inflammation, and remodeling. The increase of airway smooth muscle (ASM) mass is a fundamental component of bronchial remodeling in AA, yet the pathophysiological mechanisms and clinical outcomes associated with ASM modulation are still elusive.Objective: To compare the expression level of β-dystroglycan (β-DG) in ASM in AA subjects and a healthy control group and to investigate the relationship between eosinophils and β-DG in ASM in patients with AA.Methods: Thirteen AA patients and seven control subjects were analyzed for the ASM area and eosinophil cells. Bronchial biopsies were stained by β-DG and eosinophil cationic protein (ECP) using immunohistochemistry.Results: The proportion of ASM with β-DG staining was greater in those with AA than in the healthy control group (mean (95% CI) (28.3% (23.8–32.7%) vs. 16.4% (14.1–18.5%), P < 0.0001). The number of ECP–positive cells was higher in patients with AA than in the control group (4,056 (3,819–4,296) vs. 466 (395–537) cells/mm2 P < 0.0001). In AA, the number of ECP positive cells was significantly correlated to the β-DG expression in ASM (r = 0.77, P = 0.002).Conclusion: There is an increased β-DG expression in ASM and a higher number of ECP positive cells in the bronchial biopsy of those with AA than those in the control group. The increased expression of β-DG in ASM in AA subjects correlates with the number of eosinophils, suggesting a role for this cell in airway remodeling in AA.
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| 44. |
- Silverpil, Elin, 1978, et al.
(författare)
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Impact of Interleukin-17 on Macrophage Phagocytosis of Apoptotic Neutrophils and Particles
- 2011
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Ingår i: Inflammation. - 0360-3997. ; 34:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- There is now substantial evidence that the cytokine interleukin-17 orchestrates the accumulation of neutrophils in mammals and thereby contributes to host defense. However, the role of IL-17 in controlling neutrophil turnover is not fully understood. Here, we demonstrate that IL-17 stimulates the apoptosis of mouse neutrophils and, simultaneously, the release of the microbicidal compound, myeloperoxidase. IL-17 also stimulates mouse macrophages to phagocytose aged neutrophils and latex beads, and it induces an increase in a soluble form of the phagocytic receptor, lectin-like oxidized low-density lipoprotein receptor-1 as well. In contrast, IL-17 does not markedly increase the release of the archetype neutrophil-recruiting cytokine, macrophage inflammatory protein-2 in mouse macrophages. Importantly, IL-17 also stimulates the phagocytosis of latex beads in human monocyte-derived macrophages. Thus, IL-17 bears the potential to control both phagocytosis and neutrophil turnover during activation of host defense.
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| 45. |
- Sjögren, Florence, 1950-, et al.
(författare)
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The influence of retinoic acid and retinoic acid derivatives on Beta2 integrins and L-selectin expression in HL-60 cells in vitro
- 2000
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Ingår i: Inflammation. - 0360-3997 .- 1573-2576. ; 24:1, s. 21-32
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Tidskriftsartikel (refereegranskat)abstract
- A decreased expression of the ▀2-integrin CD11b molecules on peripheral neutrophils from patients with pustular psoriasis occurred during treatment with retinoid compounds. Since this effect could not be mimicked in vitro with isolated peripheral neutrophils, the effect of retinoid compounds on cell differentiation was investigated. The promyelocytic cell line, HL60, was used to study what effect different retinoid compounds had on the cell surface expression of CD11b and L-selectin (CD62L) molecules, complement- mediated phagocytosis, adhesion and the oxidative burst. Retinoid- differentiated cells showed a significantly lower expression of CD11b and CD62L, and a decreased phagocytosis and oxidative burst compared to DMSO- differentiated HL60 cells or peripheral blood neutrophils. The diminished expression of ▀2-integrins or L-selectin did not affect their adhesion to non-activated or lipopolysaccharide-activated endothelial cells in vitro but may however affect adhesion to vascular endothelium under shear forces during blood flow. These results suggest that retinoid treatment could affect several early steps in the inflammatory process.
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| 46. |
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| 47. |
- Spang, Christoph, et al.
(författare)
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VGluT2 and NMDAR1 expression in cells in the inflammatory infiltrates in experimentally induced myositis : evidence of local glutamate signaling suggests autocrine/paracrine effects in an overuse injury model
- 2012
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 35:1, s. 39-48
-
Tidskriftsartikel (refereegranskat)abstract
- It is not known whether a glutamate signaling system is involved in muscle inflammation (myositis). In the present study, we examined this question in the soleus muscle in a laboratory model of myositis resulting from repetitive overuse induced by electrical stimulation and injection of pro-inflammatory substances. Sections of rabbit soleus muscle with an induced myositis, i.e., exhibiting infiltration of inflammatory cells, were examined immunohistochemically using antibodies against vesicular glutamate transporter VGluT2 and the glutamate receptor NMDAR1. In situ hybridization for demonstration of VGluT2 mRNA was also performed. Specific reactions for both VGluT2 and NMDAR1 could be observed immunohistochemically in the same cells. In situ hybridization demonstrated the occurrence of VGluT2 mRNA in the cells. Double staining showed that the VGluT2 reactions were detectable in cells marked with T cell/neutrophil marker and in cells expressing eosinophil peroxidase. These data suggest the occurrence of previously unknown glutamate-mediated autocrine/paracrine effects within the inflammatory infiltrates during the development of muscle inflammation.
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| 48. |
- Thomsen, P, et al.
(författare)
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Joint fluid leukocyte activation by preformed immune complexes
- 1986
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Ingår i: Inflammation. - 0360-3997. ; 10:3, s. 243-256
-
Tidskriftsartikel (refereegranskat)abstract
- Acute synovitis was induced in rabbit knee joints by intraarticular injection of preformed bovine serum albumin (BSA) -anti BSA immune complexes (ICs). Polymorphonuclear granulocytes (PMNGs) which had migrated into joints injected with ICs were degranulated and contained ICs as revealed by electron microscopy and were activated as revealed by the measurement of chemiluminescence (CL). In contrast, leukocytes from control joints injected with BSA and normal rabbit serum as well as glycogen-elicited peritoneal leukocytes did not display any morphological changes and did not show CL. Compared to cells from other sources, leukocytes from IC joints showed a decreased CL response when stimulated in vitro with ICs but not with opsonized zymosan, suggesting a stimulus-specific modification of the PMNG responsiveness. Inhibition experiments showed that oxygen radicals and formation of arachidonate metabolites, mainly of the lipoxygenase pathway, were involved in the CL response of the IC-stimulated joint fluid PMNGs. Our observations on morphology, activity, and responsiveness of emigrated cells from the various sources suggest, together with previous observations, that the reaction of leukocytes in IC-induced synovitis consists of an initial migration phase not related to an increased CL and a subsequent activation phase characterized by degranulation, phagocytosis of ICs and increased CL.
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| 49. |
- Wagner, Michael, et al.
(författare)
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Increased Fecal Levels of Chromogranin A, Chromogranin B and Secretoneurine in Collagenous Colitis
- 2013
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Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 36:4, s. 855-861
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between the enteric nervous system and the immune system are suggested to play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aims to determine if chromogranin A (CgA), chromogranin B (CgB), and secretoneurin (SN) are detectable in feces (F) from patients with collagenous colitis (CC) and to compare the levels found in patients with ulcerative colitis (UC) and Crohn’s disease (CD) before and during treatment. Patients with CC (n = 12) were studied before and after 3, 7, 28, and 56 days of treatment. Patients with IBD (UC, n = 21; CD, n = 11) were studied before and after 28 and 56 days of treatment. Clinical data were recorded, and fecal samples were collected at each occasion. F-CgA, F-CgB, and F-SN were measured by RIA. Eleven patients with CC, 21 with UC, and 10 with CD achieved remission. On inclusion, CC patients had higher levels of F-CgA, F-CgB, and F-SN than patients with IBD and controls. Patients with IBD expressed markedly lower levels of F-SN than controls. During treatment, F-SN in CC patients decreased to control levels but remained low in IBD patients. No change was found in F-CgA or F-CgB in any of the groups. In conclusion, CgA, CgB, and SN are detectable in feces, and CC patients express higher values than patients with IBD and controls. During treatment, F-SN decreased to control levels in CC. These findings suggest that the enteric nervous system is clearly involved in the pathophysiology of CC.
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| 50. |
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