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Expression of Interleukin-26 is upregulated in inflammatory bowel disease.

ABSTRACT: AIM:To investigate interleukin (IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and the function of IL-26. METHODS:Human colonic subepithelial myofibroblasts (SEMFs) were isolated from colon tissue surgically resected. The expression of IL-26 protein and its receptor complex was analyzed by immunohistochemistry. The gene expression induced by IL-26 was evaluated by real-time polymerase chain reaction. Intracellular signaling pathways were evaluated by immunoblotting and specific small interfering (si) RNA transfection. RESULTS:The mRNA and protein expression of IL-26 were significantly enhanced in the inflamed mucosa of patients with IBD. IL-26 receptor complex was expressed in colonic SEMFs in vivo and in vitro. IL-26 stimulated the mRNA expression of IL-6 and IL-8 in colonic SEMFs. The inhibitors of mitogen-activated protein kinases and phosphoinositide 3-kinase, and siRNAs for signal transducers and activator of transcription 1/3, nuclear factor-kappa B and activator protein-1 significantly reduced the mRNA expression of IL-6 and IL-8 induced by IL-26. CONCLUSION:These results suggest that IL-26 plays a role in the pathophysiology of IBD through induction of inflammatory mediators.

SUBMITTER: Fujii M

PROVIDER: S-EPMC5558115 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Expression of Interleukin-26 is upregulated in inflammatory bowel disease.

Fujii Makoto M Nishida Atsushi A Imaeda Hirotsugu H Ohno Masashi M Nishino Kyohei K Sakai Shigeki S Inatomi Osamu O Bamba Shigeki S Kawahara Masahiro M Shimizu Tomoharu T Andoh Akira A

World journal of gastroenterology 20170801 30

<h4>Aim</h4>To investigate interleukin (IL)-26 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD) and the function of IL-26.<h4>Methods</h4>Human colonic subepithelial myofibroblasts (SEMFs) were isolated from colon tissue surgically resected. The expression of IL-26 protein and its receptor complex was analyzed by immunohistochemistry. The gene expression induced by IL-26 was evaluated by real-time polymerase chain reaction. Intracellular signaling pathways were ...[more]

PMID: 28852311

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Project description:Background and aimInterleukin-26 (IL-26) has been implicated in several chronic inflammatory diseases. However, its role in inflammatory bowel disease (IBD) remains to be elucidated. We aimed to investigate IL-26 expression in IBD and its immunoregulatory effects on macrophages.MethodsWe assessed IL-26 expression in the intestinal mucosa and blood samples of IBD patients and healthy controls (HC). The associations between the clinical characteristics of IBD and IL-26 expression levels in serum and peripheral blood mononuclear cells (PBMCs) were investigated. In addition, the transcriptional changes in THP-1 macrophages exposed to IL-26 were determined by RNA sequencing and validated with qRT-PCR, ELISA and western blots.ResultsCompared with HC, in IBD patients, IL-26 expression levels were elevated in the inflamed intestinal mucosa, and reduced in serum and PBMCs. IL-26 mRNA levels in PBMCs, but not serum IL-26 levels, were inversely correlated with disease activity in IBD. Furthermore, IL-26 mRNA levels in PBMCs were significantly lower in patients with complicated Crohn's disease. A total of 1,303 differentially expressed protein-coding genes were identified between untreated and IL-26-treated macrophages. The up-regulated genes showed enrichment in some inflammatory and immune-related processes and pathways. Additionally, GSEA showed that neutrophil, monocyte, and lymphocyte chemotaxis was significantly enriched in IL-26-treated macrophages. Further validation revealed that IL-26 promotes the secretion of multiple inflammatory cytokines and chemokines and upregulates the expression of adhesion molecules, MMP-8, and MMP-9 while inhibiting MMP-1 in macrophages.ConclusionCompared with HC, in IBD patients, IL-26 levels were elevated in the inflamed intestinal mucosa, and reduced in the peripheral blood. The transcriptional changes in macrophages exposed to IL-26 suggest that IL-26 may amplify the aberrant immune response in IBD by activating macrophages.

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Expression of Interleukin-26 is upregulated in inflammatory bowel disease.

Publications

Expression of Interleukin-26 is upregulated in inflammatory bowel disease.

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