Interleukin-10 expression in intestine of Crohn disease.

Akagi, Shinji; Hiyama, Eiso; Imamura, Yuji; Takesue, Yoshio; Matsuura, Yuichirou; Yokoyama, Takashi

doi:10.3892/ijmm.5.4.389

Cited by 14 publications

(13 citation statements)

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“…Therefore, deficiency or dysregulated expression of IL-10 production is often a main cause of autoimmune diseases or exaggerated inflammatory responses. IL-10-deficient mice as well as patients with Crohn's disease display severe chronic enterocolitis, in which the up-regulation of inflammatory cytokines such as IFN-␥, IL-12, TNF-␣, IL-1, and IL-18 is observed, demonstrating the protective role of IL-10 in inflammatory conditions (35). Systemic lupus erythematosus is associated with the high production of IL-10, which leads to impaired T cell responses and dysregulation of B cell activation (36).…”

Section: Discussionmentioning

confidence: 99%

The Production of IL-10 by Human Regulatory T Cells Is Enhanced by IL-2 through a STAT5-Responsive Intronic Enhancer in the IL-10 Locus

Tsuji-Takayama

Suzuki

Yamamoto

et al. 2008

The Journal of Immunology

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STAT5 molecules are key components of the IL-2 signaling pathway, the deficiency of which often results in autoimmune pathology due to a reduced number of CD4+CD25+ naturally occurring regulatory T (Treg) cells. One of the consequences of the IL-2-STAT5 signaling axis is up-regulation of FOXP3, a master control gene for naturally occurring Treg cells. However, the roles of STAT5 in other Treg subsets have not yet been elucidated. We recently demonstrated that IL-2 enhanced IL-10 production through STAT5 activation. This occurred in two types of human Treg cells: a novel type of umbilical cord blood-derived Treg cell, termed HOZOT, and Tr1-like Treg cells, IL-10-Treg. In this study, we examined the regulatory mechanisms of IL-10 production in these Treg cells, focusing specifically on the roles of STAT5. By performing bioinformatic analysis on the IL-10 locus, we identified one STAT-responsive element within intron 4, designated I-SRE-4, as an interspecies-conserved sequence. We found that I-SRE-4 acted as an enhancer element, and clustered CpGs around the I-SRE-4 were hypomethylated in IL-10-producing Treg cells, but not in other T cells. A gel-shift analysis using a nuclear extract from IL-2-stimulated HOZOT confirmed that CpG DNA methylation around I-SRE-4 reduced STAT5 binding to the element. Chromatin immunoprecipitation analysis revealed the in situ binding of IL-2-activated STAT5 to I-SRE-4. Thus, we provide molecular evidence for the involvement of an IL-2-STAT5 signaling axis in the expression of IL-10 by human Treg cells, an axis that is regulated by the intronic enhancer, I-SRE-4, and epigenetic modification of this element.

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Section: Discussionmentioning

confidence: 99%

The Production of IL-10 by Human Regulatory T Cells Is Enhanced by IL-2 through a STAT5-Responsive Intronic Enhancer in the IL-10 Locus

Tsuji-Takayama

Suzuki

Yamamoto

et al. 2008

The Journal of Immunology

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“…It is believed that IL-10 plays an important role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens [3] and the dysregulation of IL-10 is connected with inflammatory bowel disease [1,13]. IL-10 and IL-1 display opposite effects, the former being an inhibitor of IL-1 synthesis by macrophages.…”

Section: Discussionmentioning

confidence: 99%

Early cytokine response of gnotobiotic piglets to Salmonella enterica serotype Typhimurium

et al. 2002

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-Cytokine response against Salmonella Typhimurium is traditionally studied in conventional animals. Germ-free animals, however, enable to study response against infection without background effect of other microorganisms. Plasma and ileal inflammatory cytokines in germ-free piglets orally infected with virulent LT2 strain or, with a non-virulent SF1591 rough mutant were quantified by ELISA. In plasma and ileal washes, IFN-γ levels significantly increased in both infected groups. TNF-α and IL-18 were mostly missing in plasma 24 h after infection. In the ileum, IFN-γ, TNF-α, and IL-1β were induced mainly by the virulent strain, whereas IL-18 was induced in highest quantity by non-virulent Salmonella. These data confirmed an important role of IFN-γ, as well as other inflammatory cytokines in early stage of salmonellosis.Salmonella Typhimurium / gnotobiotic piglet / cytokine Résumé -La réponse précoce en cytokines contre Salmonella enterica Typhimurium chez des porcelets gnotobiotiques. La réponse en cytokines contre Salmonella Typhimurium est traditionnellement étudiée chez les animaux conventionnels. Les animaux sans germes, cependant, permettent d'étudier la réponse à l'infection sans avoir le bruit de fond dû à d'autres micro-organismes. Les cytokines inflammatoires du plasma et de l'iléon chez des porcelets sans germes, infectés oralement par la souche LT2 ou avec un mutant non virulent de SF1591, ont été quantifiées par ELISA. Dans le plasma et dans les lavages de l'iléon, les taux d'IFN-γ ont augmenté significativement chez les animaux des deux groupes infectés. Le TNF-α et l'IL-18 étaient présents en faibles quantités dans le plasma 24 heures après infection. Dans l'iléon, l'IFN-γ , le TNF-α et l'IL-1β ont été induits principalement par la souche virulente, alors que l'IL-18 a été induite en plus grande quantité par les salmonelles non virulentes. Ces données confirment le rôle important de l'IFN-γ et des autres cytokines inflammatoires dans les stades précoces de la salmonellose.Salmonella Typhimurium / porcelet gnotobiotique / cytokine 291 Vet. Res. 33 (2002) 291-297

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“…IL-10 has anti-inflammatory effects on proinflammatory cytokines (IL-1, IL-6, TNF-α) and its mucosal levels were found increased both in CD and UC (Akagi et al, 2000;Olsen et al, 2007) (for review see (Kaser et al, 2010)) except for a single study (Nielsen et al, 1996). Of interest, mucosal levels of IL-10 and IL-4 in UC did not correlate with the treatment effects of infliximab (Olsen et al, 2009) and were not found reduced after infliximab treatment (Agnholt et al, 2003).…”

Section: Il-10mentioning

confidence: 99%

Clinical, Biological, and Laboratory Parameters as Predictors of Severity of Clinical Outcome and Response to Anti–TNF–Alpha Treatment in Ulcerative Colitis

Olsen¹,

Florholmen²

2011

Ulcerative Colitis - Treatments, Special Populations and the Future

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Interleukin-10 expression in intestine of Crohn disease.

Cited by 14 publications

References 0 publications

The Production of IL-10 by Human Regulatory T Cells Is Enhanced by IL-2 through a STAT5-Responsive Intronic Enhancer in the IL-10 Locus

The Production of IL-10 by Human Regulatory T Cells Is Enhanced by IL-2 through a STAT5-Responsive Intronic Enhancer in the IL-10 Locus

Early cytokine response of gnotobiotic piglets to Salmonella enterica serotype Typhimurium

Clinical, Biological, and Laboratory Parameters as Predictors of Severity of Clinical Outcome and Response to Anti–TNF–Alpha Treatment in Ulcerative Colitis

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