| 1. |
- Axelsson, Jakob B, et al.
(författare)
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Proposed protective mechanism of the pancreas in the rat
- 2010
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heparan sulphate is known to have various functions in the animal body, including surveillance of tissue integrity. Administered intraperitoneally, it induces a systemic inflammatory response syndrome and when given locally in the pancreas it initiates a protective inflammatory response. The aim of the present study was to investigate the underlying mechanisms behind cell recruitment following intra-ductal infusion of heparan sulphate. Methods: Rats were subjected to intraductal-infusion of heparan sulphate, lipopolysaccharide and phosphate buffered saline into the pancreas. Pancreatic tissue was harvested 1, 3, 6, 9 or 48 hours after infusion and stained immunohistochemically for myeloperoxidase, ED-1, CINC-1 and MCP-1, as well as using eosin hematoxylin staining. Furthermore, MPO activity and MCP-1 and CINC-1 concentrations of tissue homogenates were measured. All differences were analyzed statistically using the Mann-Whitney U-test. Results: During HS infusion, a rapid influx of macrophages/monocytes, as visualized as ED-1 positive cells, was seen reaching a maximum at 6 hours. After 48 hours, the same levels of ED-1 positive cells were noted in the pancreatic tissue, but with different location and morphology. Increased neutrophil numbers of heparan sulphate treated animals compared to control could be detected only 9 hours after infusion. The number of neutrophils was lower than the number of ED-1 positive cells. On the contrary, LPS infusion caused increased neutrophil numbers to a larger extent than heparan sulphate. Furthermore, this accumulation of neutrophils preceded the infiltration of ED-1 positive cells. Chemokine expression correlates very well to the cell infiltrate. MCP-1 was evident in the ductal cells of both groups early on. MCP-1 preceded monocyte infiltration in both groups, while the CINC-1 increase was only noticeable in the LPS group. Conclusions: Our data suggest that heparan and LPS both induce host defense reactions, though by using different mechanisms of cell-recruitment. This implies that the etiology of pancreatic inflammation may influence how the subsequent events will develop.
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| 2. |
- Hansson, Emma, et al.
(författare)
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Histology of adipose tissue inflammation in Dercum's disease, obesity and normal weight controls: a case control study.
- 2011
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dercum's disease (DD) is characterised by obesity and chronic pain (> 3 months) in the adipose tissue. The pathogenesis of DD is unknown, but inflammatory components have been proposed. In previous reports and studies, an inconsistent picture of the histological appearance of the adipose tissue in DD has been described. The aim of this investigation was to examine the histological appearance of adipose tissue in patients with DD, with particular focus on inflammatory signs. METHODS: Fat biopsies were sampled from painful regions from 53 patients with DD. In 28 of the patients, a control adipose tissue biopsy was taken from a location where the patient did not experience any pain. In addition, fat biopsies were sampled from 41 healthy pain-free obese control patients and 11 healthy pain-free normal weight control patients. The extent of inflammation was evaluated on histological sections stained with haematoxylin-eosin. RESULTS: There was no statistically significant difference in the extent of inflammation between the biopsies from the painful knee and the biopsies from the non-painful area (p = 0.5), nor between the biopsies from the abdomen, and the biopsies from the non-painful area (p = 0.4), in patients with DD. A statistically significant difference in extent of inflammation was observed between DD and obese control patients regarding the abdomen (p = 0.022), but not the knee (p = 0.33). There were no differences in extent of inflammation between DD patients and normal weight controls (p = 0.81). CONCLUSION: The findings suggest that there is an inflammatory response in the adipose tissue in DD. However, this response is not more pronounced than that in healthy obese controls. This contradicts inflammation as the aetiology of DD.
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| 3. |
- Mossberg, Natalia, et al.
(författare)
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Leukocyte oxygen radical production determines disease severity in the recurrent Guillain-Barré
- 2010
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recurrent Guillain-Barré syndrome (RGBS) is characterized by at least two GBS episodes with intervening remission. In a previous study of monophasic GBS, we reported that the magnitude of oxygen radical production ("respiratory burst”) in peripheral blood leukocytes was inversely correlated to disease severity. The present study sought to establish a similar correlation in patients with RGBS. Methods: Oxygen radical production in leukocytes was induced by formyl-Met-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val- Met-NH2 (WKYMVM), or phorbol myristate acetate (PMA) and assessed by quantifying superoxide anion formed by the leukocyte NADPH oxidase. Results: Disease severity, assessed using the MRC score, was negatively correlated to superoxide anion production triggered by fMLF or WKYMVM (p = 0.001 and 0.002, respectively; n = 10). Superoxide anion production also was significantly lower in RGBS patients with incomplete recovery after stimulation with fMLF (p = 0.004) or WKYMVM (p = 0.003). Conclusion: We conclude that a lower respiratory burst in leukocytes is strongly associated with a severe course of RGBS
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| 4. |
- Olsson, Sandra, et al.
(författare)
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Different roles for non-receptor tyrosine kinases in arachidonate release induced by zymosan and Staphylococcus aureus in macrophages
- 2006
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 3:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Yeast and bacteria elicit arachidonate release in macrophages, leading to the formation of leukotrienes and prostaglandins, important mediators of inflammation. Receptors recognising various microbes have been identified, but the signalling pathways are not entirely understood. Cytosolic phospholipase A2 is a major down-stream target and this enzyme is regulated by both phosphorylation and an increase in intracellular Ca2+. Potential signal components are MAP kinases, phosphatidylinositol 3-kinase and phospholipase Cgamma2. The latter can undergo tyrosine phosphorylation, and Src family kinases might carry out this phosphorylation. Btk, a Tec family kinase, could also be important. Our aim was to further elucidate the role of Src family kinases and Btk. METHODS: Arachidonate release from murine peritoneal macrophages was measured by prior radiolabeling. Furthermore, immunoprecipitation and Western blotting were used to monitor changes in activity/phosphorylation of intermediate signal components. To determine the role of Src family kinases two different inhibitors with broad specificity (PP2 and the Src kinase inhibitor 1, SKI-1) were used as well as the Btk inhibitor LFM-A13. RESULTS: Arachidonate release initiated by either Staphylococcus aureus or yeast-derived zymosan beads was shown to depend on members of the Src kinase family as well as Btk. Src kinases were found to act upstream of Btk, phosphatidylinositol 3-kinase, phospholipase Cgamma2 and the MAP kinases ERK and p38, thereby affecting all branches of the signalling investigated. In contrast, Btk was not involved in the activation of the MAP-kinases. Since the cytosolic phospholipase A2 in macrophages is regulated by both phosphorylation (via ERK and p38) and an increase in intracellular Ca2+, we propose that members of the Src kinase family are involved in both types of regulation, while the role of Btk may be restricted to the latter type. CONCLUSION: Arachidonate release induced by either Staphylococcus aureus or zymosan was found to depend on Src family kinases as well as Btk. While members of the Src kinase family were shown to act upstream of Btk and the MAP kinases, Btk plays another role independent of MAP kinases, but down-stream of the Src family kinases.
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| 5. |
- Lucetti, Daniel L., et al.
(författare)
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Anti-inflammatory Effects and Possible Mechanism of Action of Lupeol Acetate Isolated From Himatanthus Drasticus (Mart.) Plumel
- 2010
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Ingår i: Journal of Inflammation. - : BioMed Central (BMC). - 1476-9255. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: The species Himatanthus drasticus is popularly known in Northeast Brazil as "janaguba" and belongs to the family Apocynaceae. The latex collected from its stem bark is used for several purposes including anti-inflammatory properties and presents among its bioactive constituents the pentacyclic triterpene lupeol. The objective of the present work was to study in vivo and in vitro the lupeol acetate (LA) isolated from the plant latex, in several models of inflammation.Methods: Male Swiss mice (25-30 g, 6-24 animals per group) were administered with LA, 30 min before the test initiation. In the evaluation of analgesic activity the formalin test was used. The anti-inflammatory activity was evaluated by the following tests: paw edema induced by carrageenan and dextran, and the carrageenan-induced neutrophil migration into peritoneal cavities. Furthermore, the effect of LA on the myeloperoxidase release (MPO, an inflammation biomarker) from human neutrophils was also determined, as well as its antioxidant potential by the DPPH assay.Results: In the formalin test, LA (10, 25 and 50 mg/kg, i.p.) inhibited both the 1(st) (neurogenic, 0-5 min) and mainly the 2(nd) (inflammatory, 20-25 min) phase. Naloxone completely reversed the LA effect, indicating the participation of the opioid system. LA also significantly inhibited carrageenan-and dextran-induced paw edemas, as well as the neutrophil migration to the peritoneal cavity evaluated by the carrageenan-induced pleurisia. In this model, the effect of a very low dose of LA (0.1 mg/kg) was potentiated by the same dose of pentoxifylline (PTX), a known TNF-alpha inhibitor. LA (25 and 50 mu g/ml) was also very effective in inhibiting MPO released from stimulated human neutrophils, and significantly decreased the number of cells expressing iNOS activity in the paw of mice submitted to carrageenan-induced edema, suggesting a drug involvement with the NO system.Conclusions: The anti-inflammatory effect of LA probably involves the opioid system, asindicated by the complete blockade of the opioid antagonist naloxone. Furthermore, the LA effect was potentiated by PTX (a TNFalpha inhibitor). LA also decreased the number of iNOS cells, suggesting the participation of pro-inflammatory cytokines and the NO system in the drug action.
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| 6. |
- Seifert, Oliver, et al.
(författare)
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Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions
- 2012
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Ingår i: Journal of Inflammation. - : BioMed Central. - 1476-9255. ; 9:43
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gold salts has previously been used in the treatment of rheumatoid arthritis but have been replaced by biologicals such as TNF-alpha inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These findings open the question of possible immunomodulatory effects of metallic gold and motivate efforts on a deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages. less thanbrgreater than less thanbrgreater thanMethods: Human macrophage cells (cell line THP-1) were grown on gold foils and intracellular uptake was analysed by autometallography. The impact of phagocytised gold ions on viability of THP-1 cells was investigated by trypan blue staining and TUNEL assay. The global gene expression profile of THP-1 cells after incorporation of gold ions was studied using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of secreted proteins. less thanbrgreater than less thanbrgreater thanResults: Autometallography showed intracellular uptake of gold ions into THP-1 cells. No significant effect on viability of THP-1 cells was demonstrated. Our data revealed a unique gene expression signature of dissolucytotic THP-1 cells that had taken up gold ions. A large number of regulated genes were functionally related to immunomodulation. Gold ion uptake induced downregulation of genes involved in rheumatoid arthritis such as hepatocyte growth factor, tenascin-C, inhibitor of DNA binding 1 and 3 and matrix metalloproteinase 13. less thanbrgreater than less thanbrgreater thanConclusion: The data obtained in this study offer new insights into the mode of action of gold ions and suggest for the investigation of effects on other key cells and a possible future role of metallic gold as implants in rheumatoid arthritis or other inflammatory conditions.
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| 7. |
- Åberg, Anna-Maja, et al.
(författare)
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Does carbon monoxide treatment alter cytokine levels after endotoxin infusion in pigs? : A randomized controlled study
- 2008
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 5, s. 13.-
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Carbon monoxide (CO) has recently been suggested to have anti-inflammatory properties, but data seem to be contradictory and species-specific. Thus, in studies on macrophages and mice, pretreatment with CO attenuated the inflammatory response after endotoxin exposure. On the other hand, human studies showed no effect of CO on the inflammatory response. Anti-inflammatory efficacy of CO has been shown at concentrations above 10% carboxyhaemoglobin. This study was undertaken to elucidate the possible anti-inflammatory effects of CO at lower CO concentrations. METHODS: Effects of CO administration on cytokine (TNF-alpha, IL-6, IL-1beta and IL-10) release were investigated in a porcine model in which a systemic inflammatory response syndrome was induced by endotoxin infusion. Endotoxin was infused in 20 anaesthetized and normoventilated pigs. Ten animals were targeted with inhaled CO to maintain 5% COHb, and 10 animals were controls. RESULTS: In the control group, mean pulmonary artery pressure increased from a baseline value of 17 mmHg (mean, n = 10) to 42 mmHg (mean, n = 10) following 1 hour of endotoxin infusion. Similar mean pulmonary artery pressure values were found in animals exposed to carbon monoxide. Plasma levels of all of the measured cytokines increased in response to the endotoxin infusion. The largest increase was observed in TNF-alpha, which peaked after 1.5 hours at 9398 pg/ml in the control group and at 13395 pg/ml in the carbon monoxide-exposed group. A similar peak was found for IL-10 while the IL-6 concentration was maximal after 2.5 hours. IL-1beta concentrations increased continuously during the experiment. There were no significant differences between carbon monoxide-exposed animals and controls in any of the measured cytokines. CONCLUSION: Our conclusion is that 5% COHb does not modify the cytokine response following endotoxin infusion in pigs.
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| 8. |
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| 9. |
- Alehagen, Urban, et al.
(författare)
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Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10 : a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK
- 2019
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background:Inflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation.Methods:Osteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200g/day) and coenzyme Q10 (200mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates.Results:Significantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences.Conclusion:In this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group.
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| 10. |
- Hansson, Elisabeth, 1955, et al.
(författare)
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Coupled cell networks are target cells of inflammation, which can spread between different body organs and develop into systemic chronic inflammation
- 2015
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Ingår i: Journal of Inflammation-London. - : Springer Science and Business Media LLC. - 1476-9255. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Several organs in the body comprise cells coupled into networks. These cells have in common that they are excitable but do not express action potentials. Furthermore, they are equipped with Ca2+ signaling systems, which can be intercellular and/or extracellular. The transport of small molecules between the cells occurs through gap junctions comprising connexin 43. Examples of cells coupled into networks include astrocytes, keratinocytes, chondrocytes, synovial fibroblasts, osteoblasts, connective tissue cells, cardiac and corneal fibroblasts, myofibroblasts, hepatocytes, and different types of glandular cells. These cells are targets for inflammation, which can be initiated after injury or in disease. If the inflammation reaches the CNS, it develops into neuroinflammation and can be of importance in the development of systemic chronic inflammation, which can manifest as pain and result in changes in the expression and structure of cellular components. Biochemical parameters of importance for cellular functions are described in this review.
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| 11. |
- Jacobson, Sofie, 1961-, et al.
(författare)
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Levels of mannose-binding lectin (MBL) associates with sepsis-related in-hospital mortality in women
- 2020
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Ingår i: Journal of Inflammation. - : BioMed Central (BMC). - 1476-9255. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mannose-binding lectin (MBL) mediates the innate immune response either through direct opsonisation of microorganisms or through activation of the complement system. There are conflicting data whether MBL deficiency leads to increased susceptibility to infections or not. The aim of this study was to determine if low levels of mannose-binding lectin (MBL) predict sepsis development, sepsis severity and outcome from severe sepsis or septic shock.Method: Patients aged 18 years or more with documented sepsis within 24 h after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Plasma levels MBL were determined in stored samples from health surveys (baseline) and from ICU admission (acute phase). The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined with 1300 ng/mL as cut-off for low levels.Results: We identified 148 patients (61.5% women) with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 122 also had samples from the acute septic phase. Both high MBL levels in the acute phase (odds ratio [95% confidence interval]) (2.84 [1.20-6.26]), and an increase in MBL levels from baseline to the acute phase (3.76 [1.21-11.72]) were associated with increased risk for in-hospital death in women, but not in men (0.47 [0.11-2.06]). Baseline MBL levels did not predict future sepsis, sepsis severity or in-hospital mortality.Conclusions: An increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.
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| 12. |
- Jacobsson, Sofie, et al.
(författare)
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Leptin independently predicts development of sepsis and its outcome
- 2017
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Ingår i: Journal of Inflammation. - London : BioMed Central (BMC). - 1476-9255. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sepsis is a life-threatening condition and obesity is related to the clinical outcome. The underlying reasons are incompletely understood, but the adipocyte derived hormones leptin and adiponectin may be involved.Methods: Patients aged 18 years or more with documented first time sepsis events were included in a nested case-referent study if they had participated in previous health surveys. Two matched referents free of known sepsis were identified. Circulating levels of leptin and adiponectin were determined in stored plasma, and their impact on a future sepsis event and its outcome was evaluated.Results: We identified 152 patients (62% women) with a sepsis event and a previous participation in a health survey. Eighty-three % had also blood samples from the acute event. Hyperleptinemia at health survey associated with a future sepsis event (OR 1.77, 95% CI 1.04-3.00) and with hospital death. After adjustment for BMI leptin remained associated with sepsis in men, but not in women. High levels in the acute phase associated with increased risk for in hospital death in women (OR 4.18, 95% CI 1.17-15.00), while being protective in men (OR 0.05, 95% CI 0.01-0.48). Furthermore, leptin increased more from baseline to the acute phase in men than in women. Adiponectin did not predict sepsis and did not relate to outcome.Conclusions: Hyperleptinemia independently predicted the development of sepsis and an unfavourable outcome in men, and inertia in the acute response related to worse outcome.
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| 13. |
- Karlsson, Torbjörn
(författare)
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Evaluation of a competitive hepcidin ELISA assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients
- 2017
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Ingår i: Journal of Inflammation. - : BIOMED CENTRAL LTD. - 1476-9255. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a competitive hepcidin ELISA assay was evaluated for its ability to differentiate between iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients, using the absence of stainable bone marrow iron as the diagnostic criterion for iron deficiency. In addition, correlation coefficients for hepcidin versus C-reactive protein, ferritin and interleukin-6 were determined. The optimal cut-off for hepcidin was 21 mu g/L, corresponding to sensitivity and specificity of 100% and 67%, respectively, for iron deficiency. For ferritin, a sensitivity and specificity of 91% and 83%, respectively, correspond to an optimal cut-off of 87 mu g/L. Receiver operating characteristics curve analysis revealed that ELISA analysis of hepcidin is not superior to ferritin in the diagnosis of iron deficiency in elderly anaemic patients with concurrent inflammation. Hepcidin shows a strong positive correlation with ferritin, and also correlates positively with C-reactive protein in this patient population.
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| 14. |
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| 15. |
- Malm Tillgren, Sofia, et al.
(författare)
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C57Bl/6N mice have an attenuated lung inflammatory response to dsRNA compared to C57Bl/6J and BALB/c mice
- 2023
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 20, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lower respiratory infections caused by ssRNA viruses are a major health burden globally. Translational mouse models are a valuable tool for medical research, including research on respiratory viral infections. In in vivo mouse models, synthetic dsRNA can be used as a surrogate for ssRNA virus replication. However, studies investigating how genetic background of mice impacts the murine lung inflammatory response to dsRNA is lacking. Hence, we have compared lung immunological responses of BALB/c, C57Bl/6N and C57Bl/6J mice to synthetic dsRNA.METHODS: dsRNA was administered intranasally to BALB/c, C57Bl/6N and C57Bl/6J mice once/day for three consecutive days. Lactate dehydrogenase (LDH) activity, inflammatory cells, and total protein concentration were analyzed in bronchoalveolar lavage fluid (BALF). Pattern recognition receptors levels (TLR3, MDA5 and RIG-I) were measured in lung homogenates using RT-qPCR and western blot. Gene expression of IFN-β, TNF-α, IL-1β and CXCL1 was assessed in lung homogenates by RT-qPCR. ELISA was used to analyze protein concentrations of CXCL1 and IL-1β in BALF and lung homogenates.RESULTS: BALB/c and C57Bl/6J mice showed infiltration of neutrophils to the lung, and an increase in total protein concentration and LDH activity in response to dsRNA administration. Only modest increases in these parameters were observed for C57Bl/6N mice. Similarly, dsRNA administration evoked an upregulation of MDA5 and RIG-I gene and protein expression in BALB/c and C57Bl/6J, but not C57Bl/6N, mice. Further, dsRNA provoked an increase in gene expression of TNF-α in BALB/c and C57Bl/6J mice, IL-1β only in C57Bl/6N mice and CXCL1 exclusively in BALB/c mice. BALF levels of CXCL1 and IL-1β were increased in BALB/c and C57Bl/6J mice in response to dsRNA, whereas the response of C57Bl/6N was blunt. Overall, inter-strain comparisons of the lung reactivity to dsRNA revealed that BALB/c, followed by C57Bl/6J, had the most pronounced respiratory inflammatory responses, while the responses of C57Bl/6N mice were attenuated.CONCLUSIONS: We report clear differences of the lung innate inflammatory response to dsRNA between BALB/c, C57Bl/6J and C57Bl/6N mice. Of particular note, the highlighted differences in the inflammatory response of C57Bl/6J and C57Bl/6N substrains underscore the value of strain selection in mouse models of respiratory viral infections.
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| 16. |
- Mohanty, Soumitra, et al.
(författare)
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Inhibition of COX-2 signaling favors E. coli during urinary tract infection
- 2023
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Ingår i: Journal of Inflammation. - : BioMed Central (BMC). - 1476-9255. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: To avoid the overuse of antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), acting via cyclooxygenase (COX) inhibition, have been used to reduce pain and as an alternative treatment for uncomplicated urinary tract infections (UTIs). However, clinical studies evaluating NSAIDs versus antibiotics have reported an increased risk of acute pyelonephritis. Therefore, we hypothesized that COX inhibition could compromise the innate immune response and contribute to complications in patients with uncomplicated UTI.Results: We here demonstrate that in particular COX-2 inhibition led to decreased expression of the antimicrobial peptides psoriasin and human β-defensin-2 in human uroepithelial cells. Psoriasin expression was altered in neutrophils and macrophages. COX-2 inhibition also had impact on the inflammasome mediated IL-1β expression in response to uroepithelial E. coli infection. Further, COX-2 inhibition downregulated free radicals and the epithelial barrier protein claudin 1, favoring infectivity. In addition, conditioned media from COX-2 inhibited uroepithelial cells infected with E. coli failed to activate macrophages.Conclusions: Taken together, our data suggests an adverse innate immune effect of COX-2 inhibition on uroepithelial cells during UTI.
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| 17. |
- Nilsen, Tom, et al.
(författare)
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A new turbidimetric immunoassay for serum calprotectin for fully automatized clinical analysers
- 2015
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Ingår i: Journal of Inflammation. - : Springer Science and Business Media LLC. - 1476-9255. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Serum and plasma calprotectin concentration is shown to be elevated when neutrophils are activated, and may therefore be used as a marker for inflammatory diseases. A serum calprotectin immunoassay was developed based on calprotectin values observed in samples from the intensive care unit. The polyclonal avian antibodies were raised and affinity purified with calprotectin antigens. The performance was tested and it was observed that the assay was linear in the range 0.3-24.7 mg/L, the limit of quantitation was observed to be lower than 0.3 mg/L, no antigen excess was observed up to 54 mg/L, all CVs were lower than 1.8 % in the precision study, the calibration curve stability was longer than 6 weeks, and there was no significant interference detected for haemoglobin, intralipid or bilirubin. The serum calprotectin immunoassay presented in this paper performs well within the criteria carefully set from the limited clinical experience obtained in both serum and plasma. In addition it is commutable with Bühlmann MRP8/14 ELISA.
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| 18. |
- Perez-Baos, Sandra, et al.
(författare)
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Inhibition of pSTAT1 by tofacitinib accounts for the early improvement of experimental chronic synovitis
- 2019
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Ingår i: Journal of Inflammation. - : BioMed Central (BMC). - 1476-9255. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: In order to gain insight into the early effects drawn by JAK inhibitors on intra-joint JAK/STAT-dependent signaling, we sought synovial activation of STATs and their end-products, along with their modification with tofacitinib (TOFA), at flare-up in antigen induced arthritis (AIA). New Zealand rabbits were randomly assigned to four groups –healthy controls, AIA, TOFA-treated AIA, or TOFA-treated controls–. AIA was induced with 4 weekly intra-articular ovalbumin injections in sensitized animals. TOFA (10 mg·kg− 1·day− 1) was administered for the last 2 weeks. Animals were euthanized 24 h after the last injection.Results: AIA animals showed high-grade synovitis, which was partially improved by TOFA. No effects of the treatment were found on serum C-reactive protein or on the synovial macrophage infiltration at this stage. Synovial MMP-1,-3 and -13 expression levels in treated AIA rabbits were found to drop to those of controls, while a downregulation of IL6, IFNγ and TNF was evident in treated versus untreated AIA rabbits. Concurrently, a reduction in pSTAT1 and SOCS1, but not in pSTAT3, SOCS3 or active NFκB-p65, was noted with TOFA.Conclusions: Studying the mechanism of action of immunomodulatory drugs represents a major challenge in vivo, since drug-dependent decreases in inflammation very likely mask direct effects on disease mechanisms. This study design allowed us to prevent any confounding effect resulting from reductions in the overall inflammatory status, hence assessing the true pharmacological actions of TOFA in a very severe synovitis. Our findings point to pSTAT1 and MMPs as early molecular readouts of response to this JAK inhibitor.
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| 19. |
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