Enhancement of intestinal inflammation in mice lacking interleukin 10 by deletion of the serotonin reuptake transporter

Haub, Synia; Ritze, Yvonne; Bergheim, Ina; Pabst, Oliver; Gershon, Michael D.; Bischoff, Stephan C.

doi:10.1111/j.1365-2982.2010.01479.x

Cited by 71 publications

(61 citation statements)

References 30 publications

(83 reference statements)

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“…Recently, we have shown that TPH1-deficient (TPH1 2/2 ) mice, which have significantly lower amounts of 5-HT in the gut, exhibit reduced severity of colitis in two different models of experimental colitis (induced by dextran sulfate sodium [DSS] and dinitrobenzene sulfonic acid [DNBS]), whereas replenishing 5-HT levels upregulated colitis severity (24). A proinflammatory role for 5-HT has also been demonstrated in other studies where chemicalinduced colitis or spontaneous colitis associated with an IL-10 deficiency is increased in severity when coupled with the 5-HTenhancing effects of a knockout of the serotonin reuptake transporter, SERT (25,26). We have also shown that 5-HT plays a key role in the activation of immune cells to produce proinflammatory cytokines (24,27).…”

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confidence: 98%

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Kim

Bridle

Ghia

et al. 2013

The Journal of Immunology

108

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Mucosal inflammation in conditions ranging from infective acute enteritis or colitis to inflammatory bowel disease is accompanied by alteration in serotonin (5-hydroxytryptamine [5-HT]) content in the gut. Recently, we have identified an important role of 5-HT in the pathogenesis of experimental colitis. 5-HT type 7 (5-HT7) receptor is one of the most recently identified members of the 5-HT receptor family, and dendritic cells express this receptor. In this study, we investigated the effect of blocking 5-HT7 receptor signaling in experimental colitis with a view to develop an improved therapeutic strategy in intestinal inflammatory disorders. Colitis was induced with dextran sulfate sodium (DSS) or dinitrobenzene sulfonic acid (DNBS) in mice treated with selective 5-HT7 receptor antagonist SB-269970, as well as in mice lacking 5-HT7 receptor (5-HT7−/−) and irradiated wild-type mice reconstituted with bone marrow cells harvested from 5-HT7−/− mice. Inhibition of 5-HT7 receptor signaling with SB-269970 ameliorated both acute and chronic colitis induced by DSS. Treatment with SB-269970 resulted in lower clinical disease, histological damage, and proinflammatory cytokine levels compared with vehicle-treated mice post-DSS. Colitis severity was significantly lower in 5-HT7−/− mice and in mice reconstituted with bone marrow cells from 5-HT7−/− mice compared with control mice after DSS colitis. 5-HT7−/− mice also had significantly reduced DNBS-induced colitis. These observations provide us with novel information on the critical role of the 5-HT7 receptor in immune response and inflammation in the gut, and highlight the potential benefit of targeting this receptor to alleviate the severity of intestinal inflammatory disorders such as inflammatory bowel disease.

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mentioning

confidence: 98%

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Kim

Bridle

Ghia

et al. 2013

The Journal of Immunology

108

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“…Human monocytes release different cytokines and chemokines, mainly via 5-HT 3 , 5-HT 4 and 5-HT 7 activation (35). Past studies also showed that 5-HT increase production of the pro-inflammatory cytokine IL-6 in mature Dendritic cells (DCs) via 5-HT 3 , 5-HT 4 and 5-HT 7 (8,9). And DCs are known to produce different chemokines thereby regulating the traffic of Th1 and Th2 cells into inflamed tissue (36).…”

Section: Discussionmentioning

confidence: 99%

“…More than 90% of 5-HT in the body is secreted from EC cells which are located within the mucosal mucosa, and the tryptophan hydroxylase (TPH) which in EC cells is the rate-limiting enzyme in the 5-HT synthesis process (5)(6)(7). Moreover, recent studies indicated that CD4 + T cells played an important role in the development of colonic EC cell hyperplasia in intestinal infection, and EC cells were influenced by helper T-cell subtype 1 (Th1) or subtype 2 (Th2) cytokine predominant environments (8,9). Cynaropicrin ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Analgesic activity of cynaropicrinon on post‑inflammatory irritable bowel syndrome visceral hypersensitivity in a rat model

et al. 2017

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Abstract. Visceral hypersensitivity is one of the most common symptoms in patients with post-inflammatory-irritable bowel syndrome (PI-IBS). Enterochromaffin (EC) cells and 5-hydroxytryptamine (5-HT) are important in the development of visceral hyperalgesia, and EC cells are influenced by helper T-cell subtype 1 or 2 cytokine predominant environments. In the present study, the analgesic effect of cynaropicrin and its underlying mechanism on the treatment of trinitrobenzene sulfonic (TNBS)-induced PI-IBS visceral hyperalgesia rats was investigated. The results from the abdominal withdrawal reflex tests and electromyography recordings indicated that treatment with cynaropicrin significantly and dose-dependently alleviated the visceral hyperalgesia of PI-IBS rats (P<0.05). In addition, the increased colonic 5-HT content, colonic tryptophan hydroxylase expression, EC cell number and the cytokine levels, including tumor necrosis factor-α and interleukin-6 in PI-IBS rats were significantly alleviated by cynaropicrin (P<0.05). These data demonstrate that the analgesic activity of cynaropicrin on TNBS-induced PI-IBS visceral hypersensitive rats was mediated via reduction of cytokines levels. Thus, cynaropicrin as a bioactive natural product may offer promising therapeutic avenues for visceral hypersensitivity in IBS.

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“…The cytokine IL-10 suppresses the expression of Th1-derived cytokines and plays as an important immune regulator in the intestinal tract 22 . Cellular gene therapy remains highly investigational, difficult, and expensive…”

Section: Discussionmentioning

confidence: 99%

Relationship between IL-10 gene -819C/T polymorphism and the risk of inflammatory bowel disease: A meta-analysis

Guo

et al. 2016

Afr H. Sci.

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Background: The -819C/T polymorphism in interleukin 10 (IL-10) gene has been reported to be associated with inflammatory bowel disease (IBD) ,but the previous results are conflicting. Materials and methods: The present study aimed at investigating the association between this polymorphism and risk of IBD using a meta-analysis.PubMed,Web of Science,EMBASE,google scholar and China National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant publications from their inception to April 2016.Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models. Results: A total of 7 case-control studies containing 1890 patients and 2929 controls were enrolled into this meta-analysis, and our results showed no association between IL-10 gene -819C/T polymorphism and IBD risk(TT vs. CC:OR=0.81,95%CI 0.64-1.04;CT vs. CC:OR=0.92,95%CI 0.81-1.05; Dominant model: OR=0.90,95%CI 0.80-1.02; Recessive model: OR=0.84,95%CI 0.66-1.06). In a subgroup analysis by nationality, the -819C/T polymorphism was not associated with IBD in both Asians and Caucasians. In the subgroup analysis stratified by IBD type, significant association was found in Crohn's disease(CD)(CT vs. CC:OR=0.68,95%CI 0.48-0.97). Conclusion: In summary, the present meta-analysis suggests that the IL-10 gene -819C/T polymorphism may be associated with CD risk.

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Enhancement of intestinal inflammation in mice lacking interleukin 10 by deletion of the serotonin reuptake transporter

Cited by 71 publications

References 30 publications

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Analgesic activity of cynaropicrinon on post‑inflammatory irritable bowel syndrome visceral hypersensitivity in a rat model

Relationship between IL-10 gene -819C/T polymorphism and the risk of inflammatory bowel disease: A meta-analysis

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