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

ABSTRACT

Abstract Objectives: M1 macrophage polarization and phenotype in Inflammatory Bowel Disease (IBD) are common biological responses. Method: Herein, IBD mice models were constructed and macrophages were derived. Results: It 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 pheno-type and prevent M1 macrophage polarization via inhibiting FGL2 in vitro, and miR-146b overexpression alleviated the intestinal injury of IBD mice in vivo. Conclusions: Overall, it is potential to use miR-146b for the amelioration of IBD. HIGHLIGHTS miR-146b was downregulated in Inflammatory Bowel Disease (IBD) mice and LPS-induced macrophages. Fibrinogen Like 2 (FGL2) was identified as the target gene of miR-146b. miR-146b ameliorated the inflammation and blocked M1 macrophage polarization via inhibiting FGL2. miR-146b ameliorated the symptoms and pathological injury of IBD via inhibiting FGL2.