Differential expression of Toll-like receptor 4, F4/80 and pro-inflammatory cytokines in mucosa and mesenteric fat tissue of Crohnʼs disease patients

Leal, Raquel Franco; Milanski, Marciane; Lourdes, María de; Ayrizono, S.; Fagundes, João José; Coope, Andressa; Portovedo, Mariana; Rodrigues, Viviane Soares; Coy, Cláudio Saddy Rodrigues; Velloso, Lı́cio A.

doi:10.1097/00054725-201112002-00270

Cited by 7 publications

(7 citation statements)

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“…F4/80 macrophages have been found to express higher levels of the Th1 cytokine IL-12 in inflammatory skin tissues than in healthy skin tissues [42]. F4/80 macrophages in the intestinal mucosa in Crohn’s disease patients were found to be much higher than in healthy individuals [43]. Our present results show that F4/80 macrophages had much higher IL-17 expression in the cell cultures stimulated by LPS than in the unstimulated cell cultures.…”

Section: Discussionsupporting

confidence: 46%

Interleukin-10 attenuation of collagen-induced arthritis is associated with suppression of interleukin-17 and retinoid-related orphan receptor γt production in macrophages and repression of classically activated macrophages

Liang

Wen

et al. 2014

Arthritis Res Ther

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IntroductionOur objective in the present study was to determine the signaling pathway of interleukin 10 (IL-10) for modulating IL-17 expression in macrophages and the importance of this mediation in collagen-induced arthritis (CIA).MethodsIL-10-knockout (IL-10−/−) mice and wild-type (WT) mice were immunized with chicken type II collagen (CII) to induce arthritis. The expression levels of IL-17 and retinoid-related orphan receptor γt (RORγt) in macrophages and joint tissues of IL-10−/− and WT mice were analyzed by enzyme-linked immunosorbent assay, quantitative RT-PCR (qRT-PCR) and Western blotting. The F4/80 macrophages and positive IL-17-producing macrophages in synovial tissues of the mice were determined by immunohistochemistry. The populations of classically activated macrophage (M1) and alternatively activated macrophage (M2) phenotypes were analyzed by flow cytometry. The expression of genes associated with M1 and M2 markers was analyzed by qRT-PCR.ResultsCompared to WT mice, IL-10−/− mice had exacerbated CIA development, which was associated with increased production of T helper 17 cell (Th17)/Th1 proinflammatory cytokines and CII-specific immunoglobulin G2a antibody after CII immunization. Macrophages in IL-10−/− mice had increased amounts of IL-17 and RORγt compared with the amounts in WT mice with CIA. Immunofluorescence microscopy showed that the number of IL-17-producing macrophages in synovial tissues was significantly higher in IL-10−/− mice than in WT mice. IL-10 deficiency might promote macrophage polarization toward the proinflammatory M1 phenotype, which contributes to the rheumatoid arthritis inflammation response.ConclusionIL-10 inhibits IL-17 and RORγt expression in macrophages and suppresses macrophages toward the proinflammatory M1 phenotype, which is important for the role of IL-10 in mediating the pathogenesis of CIA.

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Section: Discussionsupporting

confidence: 46%

Interleukin-10 attenuation of collagen-induced arthritis is associated with suppression of interleukin-17 and retinoid-related orphan receptor γt production in macrophages and repression of classically activated macrophages

Liang

Wen

et al. 2014

Arthritis Res Ther

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“…Regarding IL-6, its expression is increased in the mesenteric adipose tissue in TNBS colitis and inflammation is accompanied by macrophage infiltration ( 60 , 61 ). However, in inflamed mesenteric adipose tissue of CD patients IL-6 expression seems not to be significantly higher than in other inflammatory conditions like colorectal cancer (CC) or diverticulitis ( 67 , 82 ).…”

Section: Working Modelmentioning

confidence: 86%

Bacterial Translocation – Impact on the Adipocyte Compartment

2014

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Over the last decade it became broadly recognized that adipokines and thus the fat tissue compartment exert a regulatory function on the immune system. Our own group described the pro-inflammatory function of the adipokine leptin within intestinal inflammation in a variety of animal models. Following-up on this initial work, the aim was to reveal stimuli and mechanisms involved in the activation of the fat tissue compartment and the subsequent release of adipokines and other mediators paralleled by the infiltration of immune cells. This review will summarize the current literature on the possible role of the mesenteric fat tissue in intestinal inflammation with a focus on Crohn’s disease (CD). CD is of particular interest in this context since the transmural intestinal inflammation has been associated with a characteristic hypertrophy of the mesenteric fat, a phenomenon called “creeping fat.” The review will address three consecutive questions: (i) What is inducing adipocyte activation, (ii) which factors are released after activation and what are the consequences for the local fat tissue compartment and infiltrating cells; (iii) do the answers generated before allow for an explanation of the role of the mesenteric fat tissue within intestinal inflammation? With this review we will provide a working model indicating a close interaction in between bacterial translocation, activation of the adipocytes, and subsequent direction of the infiltrating immune cells. In summary, the models system mesenteric fat indicates a unique way how adipocytes can directly interact with the immune system.

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“…However, under inflammatory conditions, TLR4 is highly increased markedly in intestinal epithelial cells, which further exacerbate the inflammatory response. Related reports have demonstrated that TLR4 is expressed in the murine intestinal mucosa, and similar to human CD, its expression is upregulated in the inflamed colon [ 34 ]. Therefore, increased expression of epithelial TLR4 is associated with the gut inflammation in CD.…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of Lipopolysaccharide and 1,3‐β‐D‐Glucan Refer to the Severity in Patients with Crohn’s Disease

Guo

Zhou

et al. 2015

Mediators of Inflammation

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Objectives. Interactions between the host and gut microbial community contribute to the pathogenesis of Crohn's disease (CD). In this study, we aimed to detect lipopolysaccharide (LPS) and 1,3-β-D-glucan (BG) in the sera of CD patients and clarify the potential role in the diagnosis and therapeutic approaches. Materials and Methods. Serum samples were collected from 46 patients with active CD (A-CD), 22 CD patients at remission stage (R-CD), and 20 healthy controls, and the levels of LPS, BG, and TNF in sera were determined by ELISA. Moreover, sixteen patients with A-CD received anti-TNF monoclonal antibody therapy (infliximab, IFX) at a dose of 5 mg/kg body weight at weeks 0, 2, and 6, and the levels of LPS and BG were also tested at week 12 after the first intravenous infusion. Results. Serum levels of LPS and BG were found to be markedly increased in A-CD patients compared with R-CD patients and healthy controls (P < 0.05). They were also observed to be positively correlated with CDAI, ESR, and SES-CD, respectively (P < 0.05). Furthermore, the levels of TNF in sera had a significant correlation with LPS and BG, respectively. The concentrations of LPS and BG were demonstrated to be significantly downregulated in the sera of A-CD patients 12 weeks after IFX treatment (P < 0.05), suggesting that blockade of TNF could inhibit bacterial endotoxin absorption, partially through improving intestinal mucosal barrier. Conclusions. Serum levels of LPS and BG are significantly increased in A-CD patients and positively correlated with the severity of the disease. Blockade of intestinal mucosal inflammation with IFX could reduce the levels of LPS and BG in sera. Therefore, this study has shed some light on measurement of serum LPS and BG in the diagnosis and treatment of CD patients.

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Differential expression of Toll-like receptor 4, F4/80 and pro-inflammatory cytokines in mucosa and mesenteric fat tissue of Crohnʼs disease patients

Cited by 7 publications

References 0 publications

Interleukin-10 attenuation of collagen-induced arthritis is associated with suppression of interleukin-17 and retinoid-related orphan receptor γt production in macrophages and repression of classically activated macrophages

Interleukin-10 attenuation of collagen-induced arthritis is associated with suppression of interleukin-17 and retinoid-related orphan receptor γt production in macrophages and repression of classically activated macrophages

Bacterial Translocation – Impact on the Adipocyte Compartment

Serum Levels of Lipopolysaccharide and 1,3‐β‐D‐Glucan Refer to the Severity in Patients with Crohn’s Disease

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