| 1. |
- Alm, Ann-Sophie, et al.
(author)
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Varying susceptibility of pulmonary cytokine production to lipopolysaccharide in mice.
- 2010
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In: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 49, s. 256-263
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Journal article (peer-reviewed)abstract
- Objectives: The lipopolysaccharide (LPS)-induced acute lung injury (ALI) model has been widely applied for pathophysiological and pharmacological research. The aim of present study is to understand the variation of acute pulmonary inflammation between mouse strains. Methods: The present study investigated the susceptibility of acute production of inflammatory mediators, e.g. cytokines, chemokines and others, to LPS in C57BL/6J, Balb/cJ, DBA/1J, CD-1, NMRI, DBA/2J, A/J, and C3H/HeN mice. Results: The susceptibility to intra-tracheal challenge with LPS varied between measured variables, durations and strains. General lung hyper-reactive susceptibility to LPS-induced pulmonary production of 6-8 inflammatory mediators followed the order NMRI, Balb/cJ, C3H/HeN, A/J, C57BL/6J, DBA/1J, DBA/2J and CD-1 mice at 4h, and A/J, C3H/HeN, CD-1, NMRI, C57BL/6J, Balb/cJ, DBA/2J and DBA/1J mice at 24h. Conclusions: Our data provide information for scientists to consider the proper strain of mice for the measurement of specific inflammatory mediators and to select sensitive or resistant mouse strains for understanding genetic variation in the pathogenesis and for the screening of target-oriented drug development.
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| 2. |
- Almqvist, Sofia, 1980, et al.
(author)
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Amelogenins modulate cytokine expression in LPS-challenged cultured human macrophages.
- 2012
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In: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 58:2, s. 274-9
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Journal article (peer-reviewed)abstract
- Amelogenins are enamel matrix proteins with a proven ability to restore tissues in patients with advanced periodontitis and chronic skin wounds. To explore the mechanisms of action of amelogenins in wound inflammation, the in vitro effect on the expression of selected cell mediators involved in inflammation and tissue repair from human monocyte-derived macrophages was studied. Macrophages were treated with amelogenins in serum-enriched medium with simultaneous lipopolysaccharide (LPS) stimulation, for 6, 24 and 72 h, and the conditioned culture medium was analysed for 28 different cytokines. Amelogenin treatment directed the LPS-induced release of both pro- and anti-inflammatory cytokines towards an alternatively activated macrophage phenotype. This change in activation was also demonstrated by the amelogenin-induced secretion of alternative macrophage activation-associated CC chemokine-1 (AMAC-1, also known as CCL18; p<0.001), a well-documented marker of alternative activation. Amelogenins were also shown significantly to increase the macrophage expression of vascular endothelial growth factor and, to a lesser but significant extent, insulin-like growth factor-1 after 24h of culture. The results of the present in vitro study show that monocyte-derived macrophages stimulated by inflammatory agonist LPS respond to the treatment with amelogenins by reducing the pro-inflammatory activity and increasing the expression of tissue repair mediators.
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| 3. |
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| 4. |
- Bay-Richter, Cecilie, et al.
(author)
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Aldosterone synergizes with peripheral inflammation to induce brain IL-1β expression and depressive-like effects.
- 2012
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In: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 60:3, s. 749-754
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Journal article (peer-reviewed)abstract
- Recent findings have shown that the physiological functions of the hormone aldosterone go far beyond its well-known role in blood-pressure regulation and salt/water homeostasis. Aldosterone is for example involved in the regulation of inflammation, and also binds directly to mineralocorticoid receptors in specific brain regions. Interestingly, depressive symptoms appear to correlate with alterations of the aldosterone system but the underlying mechanisms have not been elucidated. In this study aldosterone (2μg/100g body weight/day) was continuously administered via osmotic minipumps for 5days. Lipopolysaccharide (LPS) was administered once a day for 5days in a dose of 1mg/kg ip. The rats were tested for depressive-like behavior 24h after the last LPS injection. Protein levels of cytokines were measured in serum and cerebrospinal fluid (CSF). mRNA expression of interleukin (IL)-1β and IL-6 in the prefrontal cortex (PFC) was analyzed using reverse transcriptase qPCR. We found that aldosterone treatment increased LPS-induced IL-1β mRNA expression in the PFC and CSF. Moreover, there was a positive correlation between IL-1β in CSF and depressive-like behaviors. These findings suggest that IL-1β is affected by the renin-aldosterone-angiotensin system (RAAS) activity and connected to symptoms of depression.
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| 5. |
- Belibasakis, Georgios N., et al.
(author)
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Aggregatibacter actinomycetemcomitans targets NLRP3 and NLRP6 inflammasome expression in human mononuclear leukocytes
- 2012
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In: Cytokine. - : Elsevier. - 1043-4666 .- 1096-0023. ; 59:1, s. 124-130
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Journal article (peer-reviewed)abstract
- Periodontitis is an inflammatory condition that destroys the tooth-supporting tissues, as a result of local bacterial infection. Aggregatibacter actinomycetemcomitans is a Gram-negative facultative anaerobic species, highly associated with aggressive periodontitis. Periodontal inflammation is dominated by cytokines of the Interleukin (IL)-1 family. Prior to their secretion by mononuclear cells, IL-1 cytokines are processed by intracellular protein complexes, known as "inflammasomes", which can sense the bacterial challenge. The aim of this study was to investigate which inflammasomes are regulated in mononuclear cells in response to A. actinomycetemcomitans. The D7SS strain and its derivative leukotoxin and cytolethal distending toxin knock-out mutant strains were used to infect human mononuclear cells at a 1:10 cell: bacteria ratio, for 3h. The expression of various inflammasome components in the cells was investigated by TaqMan quantitative real-time polymerase chain reaction (qPCR). The expressions of NOD-like receptor protein (NLRP)1, NLRP2 and Absent In Melanoma (AIM)2 inflammasome sensors, as well as their effector Caspase-1 were not affected. However, NLRP3 was up-regulated, while NLRP6 was down-regulated. This effect was not dependent on the leukotoxin or the cytolethal distending toxin, as demonstrated by the use of specific gene knock-out mutant strains. IL-1β and IL-18 expressions were also up-regulated by the bacterial challenge. In conclusion, A. actinomycetemcomitans enhances NLRP3 and reduces NLRP6 inflammasome expression, irrespective of its major virulence factors, confirming the high pathogenic profile of this species, and providing further insights to the mechanisms of periodontal inflammation.
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| 6. |
- Björkander, Sofia, et al.
(author)
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Pregnancy-associated inflammatory markers are elevated in pregnant women with systemic lupus erythematosus
- 2012
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In: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 59:2, s. 392-399
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Journal article (peer-reviewed)abstract
- During normal pregnancy a dampening in T cell-mediated immunity is compensated by an increased pro-inflammatory activity. Likewise, the autoimmune disease systemic lupus erythematosus (SLE) is associated with inflammatory activity and pregnancy complications occur frequently in women with SLE. The aim of this study was to elucidate how SLE influences the chemokine and cytokine balance during and after pregnancy. Blood samples were taken from pregnant women with or without SLE at second and third trimester and 8-12 weeks after pregnancy. Cytokines (interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, TNF, IFN-gamma and IFN-alpha), chemokines (CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CCL2/MCP-1, CCL5/RANTES and CCL17/TARC), soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (gp130) were measured in serum using cytometric bead array (CBA) or enzyme-linked immunosorbent assay (ELISA). Women with SLE had increased serum concentrations of CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10 and IL-10 compared to controls both during and after pregnancy. Further, when dividing the patients based on disease activity, the women with active disease had the highest levels. Importantly, women with SLE seemed to respond to pregnancy in a similar way as controls, since the changes of cytokines and chemokines over the course of pregnancy were similar but with overall higher levels in the patient group. In conclusion, changes in pro- and anti-inflammatory serum components during pregnancy in women with SLE, occurring on top of already more pro-inflammatory levels, might increase their risk for pregnancy complications and flares. How their children are affected by this heightened inflammatory milieu during pregnancy needs further investigation.
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| 7. |
- Björnfot Holmström, Sofia, et al.
(author)
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MMP-12 and S100s in saliva reflect different aspects of periodontal inflammation
- 2019
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In: Cytokine. - : Academic Press. - 1043-4666 .- 1096-0023. ; 113, s. 155-161
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Journal article (peer-reviewed)abstract
- Matrix metalloproteinase (MMP)-12, S100A8/A9, and S100A12 are involved in innate immune responses. We addressed whether different aspects of oral health and non-disease-related covariates influence their levels in saliva. 436 participants were clinically examined, completed a health questionnaire, and provided stimulated saliva. Salivary levels of MMP-12, S100A8/A9, and S100A12 were determined by enzyme-linked immunosorbent assays. Lower MMP-12 levels were observed in individuals 40-64years old (yo) compared to < 40yo, and higher S100A8/A9 levels were found in individuals > 64yo compared to 40-64yo. Smokers exhibited lower MMP-12 and S100A12 levels compared to non-smokers. All three proteins were elevated in individuals with bleeding on probing (BOP)>20% compared to those with BOP/= 10% gingival pocket depths (PPD)>/=4mm compared to the ones with shallow pockets < 4mm. The extent of alveolar bone loss or presence of manifest caries did not alter any of the markers. MMP-12, S100A8/A9, and S100A12 levels were higher in participants with high periodontal inflammatory burden. All three proteins correlated positively to BOP, PPD, and to several inflammatory mediators. The explanatory variables for MMP-12 in saliva were age, smoking, presence of any tumor, and percentage of PPD>/=4mm. The determinant of salivary S100A8/A9 was percentage of BOP, while S100A12 levels were associated with percentage of BOP and presence of any tumor. Taken together, MMP-12 and the S100/calgranulin levels in saliva reflect different aspects of periodontal inflammation. Smoking and age should be taken into account in further investigation of these proteins as biomarker candidates of periodontal disease.
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| 8. |
- Bruhn, Sören, 1976-, et al.
(author)
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Combining gene expression microarray- and cluster analysis with sequence-based predictions to identify regulators of IL-13 in allergy
- 2012
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In: Cytokine. - : Elsevier. - 1043-4666 .- 1096-0023. ; 60:3, s. 736-740
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Journal article (peer-reviewed)abstract
- The Th2 cytokine IL-13 plays a key role in allergy, by regulating IgE, airway hyper secretion, eosinophils and mast cells. In this study, we aimed to identify novel transcription factors (TFs) that potentially regulated IL-13. We analyzed Th2 polarized naïve T cells from four different blood donors with gene expression microarrays to find clusters of genes that were correlated or anti-correlated with IL13. These clusters were further filtered, by selecting genes that were functionally related. In these clusters, we identified three transcription factors (TFs) that were predicted to regulate the expression of IL13, namely CEBPB, E2F6 and AHR. siRNA mediated knockdowns of these TFs in naïve polarized T cells showed significant increases of IL13, following knockdown of CEBPB and E2F6, but not AHR. This suggested an inhibitory role of CEBPB and E2F6 in the regulation of IL13 and allergy. This was supported by analysis of E2F6, but not CEBPB, in allergen-challenged CD4+ T cells from six allergic patients and six healthy controls, which showed decreased expression of E2F6 in patients. In summary, our findings indicate an inhibitory role of E2F6 in the regulation of IL-13 and allergy. The analytical approach may be generally applicable to elucidate the complex regulatory patterns in Th2 cell polarization and allergy.
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| 9. |
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| 10. |
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