Alcohol promotes macrophage M2b polarization in colitis by modulating the TRPV1-MAPK/NF-kB pathways
Macrophages are key immune cells in inflammatory bowel disease (IBD) that can exhibit different phenotypes and promote inflammation. Alcohol consumption is associated with increased risk and severity of IBD. We performed in vitro and in vivo experiments with dextran sodium sulfate-induced mice colitis model, peritoneal macrophages and RAW264.7 cell line to investigate the effect and mechanism of alcohol on macrophages in colitis. Our study has found that alcohol exacerbates colitis in mice, increases the aggregation of colonic macrophages, and promotes the production of various inflammatory factors. Alcohol increases lipopolysaccharides (LPS)-induced calcium influx in macrophages, which is inhibited by the TRPV1 antagonist Capsazepine (CPZ). Alcohol and LPS together induce M2b polarization of macrophages and promote the phosphorylation and nuclear translocation of P38, ERK1/2 and NF-?B, and could be inhibited by CPZ and NOD2 inhibitor. Thus, alcohol can aggravate experimental colitis in mice and promote macrophage M2b polarization through the TRPV1-MAPK/NF-kB pathways. Overall design: Peritoneal macrophages used for RNA-seq were cultured with RPMI 1640 with 1% streptomycin and penicillin for 1 h to keep the cell state consistent and stimulated by LPS 1µg/mL, LPS 1µg/mL with 5% EtOH, LPS 1µg/mL with CPZ 100 µM for 4 h.