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P001. miR-301a and miR-301b are highly expressed in inflamed mucosa of inflammatory bowel disease and promotes Th1/Th17 immune responses

R. Wu, W. Wu, Z. Liu, Shanghai Tenth People's Hospital, Tongji University, Department of Gastroenterology, Shanghai, China

Background

The altered expression of microRNAs (miR) has been associated with inflammatory bowel disease (IBD). Understanding the role of miR in IBD may lead to future insights into IBD pathogenesis. In this study, microRNA-301 (miR-301) was investigated and explored the potential role in the immune-regulation of the pathogenesis of IBD.

Methods

Expression of miR-301a and miR-301b in the serum, peripheral blood mononuclear cells (PBMC) and inflamed mucosa of IBD patients at different stages of diseases was detected by real-time PCR. Twelve CD patients were treated with anti-TNF mAb (infliximab) at weeks 0, 2, and 6, and miR-301a and miR301b were also determined in inflamed intestinal mucosa at week 10 after initial infliximab therapy. CD4+ T cells were isolated from peripheral blood of IBD patients and stimulated with anti-CD3 + anti-CD28 in the presence of inhibitor-miRNA-301a or mimics-miRNA-301a for 48h in vitro. The transcription factors of proinflammatory cytokines in CD4+ T cells were also then detected by real-time PCR.

Results

Expression of miR-301a and miR-301b was significantly increased in inflamed mucosa, serum and PBMC of CD and UC patients compared with healthy donors (P < 0.05). No statistical difference was present between UC and CD groups (P > 0.05). Expression of miRNA-301a/b was observed to be markedly decreased in inflamed mucosa 10 weeks after infliximab induction therapy compared with that before infliximab therapy (P < 0.05). Interestingly, miR-301a inhibitor was found to significantly downregulate mRNA expression of IL-17A, RORC, and TNF in IBD CD4+ T cells, while miR-301a mimics could markedly promote their expression in IBD CD4+ T cells in vitro (P < 0.05).

Conclusion

miR-301a and miR-301b are found to be highly increased in inflamed mucosa, serum, and PBMC of IBD patients. miRNA-301a promotes proinflammatory cytokine production (e.g., TNF) and Th17 cell differentiation in inflamed mucosa of IBD. Therefore, miRNA-301a may become an effective therapeutic target for treatment of human IBD.