Abstract
The primary pathophysiological alteration caused by inflammatory bowel disease (IBD) is prolonged, excessive inflammatory response to stimulation factors, which leads to intestinal mucosal lesions. microRNA (miR)-146a-5p is broadly activated in the mucosal immune response. At present, the biogenesis, function and role of miR-146a-5p in intestinal epithelial cells (IECs) during the pathogenesis of IBD remain elusive. The human colon cancer epithelial Caco-2 cell line was cultured with 10 ng/ml recombinant human IL-1β for 3 h to establish an in vitro IECs inflammatory model. Relative levels of miR-146a-5p and inflammatory factors (IL-6, IL-1β, TNF-α and IP-10) were measured by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Transfection of miR-146a-5p mimic or inhibitor into Caco-2 cells was performed to identify the influence of miR-146a-5p on Caco-2 cell inflammatory factors expression. The targeting relationship between miR-146a-5p and interleukin 1 receptor associated kinase 1 (IRAK1)/tumor necrosis factor receptor-associated factor 6 (TRAF6) was predicted by TargetScan 8.0. The present study demonstrated that miR-146a-5p and inflammatory factors (IL-6, IL-1β, TNF-α and IP-10) were upregulated in a dose- and time-dependent manner in IL-1β-stimulated Caco-2 cells. Moreover, upregulation of miR-146a-5p negatively regulated the expression of inflammatory factors, but the downregulation of miR-146a-5p increased their expression. The results of the present study demonstrated that miR-146a-5p decreased the expression of the inflammatory factors through targeted downregulation of IRAK1/TRAF6. These results suggest that miR-146a-5p negatively regulates the IL-1β-stimulated inflammatory response via downregulation of the IRAK1/TRAF6 signaling pathway in human IECs. Therefore, miR-146a-5p may act as an important diagnostic biomarker and treatment target of IBD.