OC-162 The role of micrornas MIR-31 AND MIR-155 in the deregulation of the IL-13 pathway in ulcerative colitis
- Resource Type
- Academic Journal
- Authors
- Gwiggner, M; Claridge, A; Cummings, F; Sanchez-Elsner, T
- Source
- Gut. Jul 01, 2012 61(Suppl_2 Suppl 2):A69-A70
- Subject
- Language
- English
- ISSN
- 0017-5749
INTRODUCTION: Ulcerative colitis (UC) is an inflammatory disease of the colonic mucosa driven by a Th2-like response in which IL-13 leads to toxic effects to the mucosa and activation of the IL-13/STAT6 pathways. Inhibition of STAT6 activation has been shown to reduce the inflammatory response in UC. MicroRNAs are small non-coding RNAs inhibiting gene expression by pairing to the 3’ UnTranslated Region (3’UTR) of their target mRNAs facilitating their translational repression/degradation. MiR-31 and miR-155 have been shown to be up-regulated in active UC and are involved in the regulation of innate and adaptive immune responses. Both microRNAs have been identified to target IL13Rα1. METHODS: Paired biopsies from inflamed and non-inflamed areas of the sigmoid colon were taken in 11 UC patients. MicroRNA expression and mRNA expression of IL-13 dependant genes were assessed by qPCR. In vitro experiments on a human colonic cell line (HT-29 cells) and a macrophage/monocytic cell line (THP-1 cells) were stimulated with IL-13. SOCS1 and IL13Rα1 mRNA expression were measured by qPCR in the presence or absence of transfection with pre-miR-31, pre-miR-155 or a combination of both. Data were analysed using the Wilcoxon matched pairs test. RESULTS: Our data shows a significant up-regulation of miR-31 and miR-155, as well as significant increase of IL-13 dependant mRNA expression of CCL18, SOCS1, Serpine and MMP-9 and a decrease of IL13Rα1 mRNA expression by 30% in the active segments of UC as compared to inactive disease. In vitro experiments on HT-29 cells and on THP-1 cells showed a marked reduction of mRNA expression of SOCS1 and IL13Rα1 in both cell types after treatment with pre-miR-31 and pre-miR-155 and their combination at a quarter of the original dose of each single pre-miR was equally efficacious. CONCLUSION: Our data reveals a clear up-regulation of miR-31 and miR-155 in inflamed UC as compared to neighbouring inactive tissue in the same patient. IL-13 dependant mRNA expression is also significantly increased in the same samples. The fact that IL13Rα1 mRNA expression is down-regulated in active disease in the presence of high levels of miR-31 and miR-155 may indicate a protective role for these microRNAs attempting to reduce IL13Rα1 expression and therefore the STAT6 pathway activation by IL-13 through IL13Rα1. Reduction of IL13Rα1 mRNA expression in our in vitro models transfected with pre-miRs confirms this finding. Interestingly the combination of the two microRNAs at lower doses achieving the same effect may indicate a possible synergy of action. MicroRNAs targeting IL13Rα1 in UC could have a potential therapeutic effect by down-regulation of the IL-13/STAT6 pathway and combination of microRNAs may have a synergistic effect. COMPETING INTERESTS: None declared.