MiR-146b suppresses LPS-induced M1 macrophage polarization via inhibiting the FGL2-activated NF-κB/MAPK signaling pathway in inflammatory bowel disease

Abstract

ObjectivesM1 macrophage polarization and phenotype in Inflammatory Bowel Disease (IBD) are common biological responses. MethodHerein, IBD mice models were constructed and macrophages were derived. ResultsIt was discovered that microRNA-146b (miR-146b) was downregulated in IBD mice and Lipopolysaccharide (LPS)-induced macrophages. Moreover, the inhibitory role of overexpressed miR-146b in reducing the inflammation level and blocking M1 macrophage polarization was confirmed. Further investigation indicated that Fibrinogen Like 2 (FGL2) acted as the target gene of miR-146b, and FGL2 mediated activation of NLRP3, NF-κB-p65, and p38-MAPK. More importantly, it was validated that miR-146b could ameliorate inflammatory phenotype and prevent M1 macrophage polarization via inhibiting FGL2 in vitro, and miR-146b overexpression alleviated the intestinal injury of IBD mice in vivo. ConclusionsOverall, it is potential to use miR-146b for the amelioration of IBD.