Cannabinoid CB2 receptors protect against ulcerative colitis by regulating macrophage polarization in mice / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the immunological mechanism of cannabinoid receptor CB2 in ulcerative colitis (UC) by regulating macrophage polarization so as to provide new ideas for the development of new drugs and treatment of the disease. Methods: Human UC specimens were immunohistochemically stained with macrophage mark CD68. Male ICR mice were made into ulcerative colitis model by dextran sulfate sodium DSS. After treatment with CB2 receptor agonist JWH133, the weight of the mice and the inflammatory activity indexes (DAI) (diarrhea and bloody stool) of UC were recorded, and the intestinal tissues were collected. The degree of inflammation and polarity of macrophages of intestinal tract were analyzed with HE staining and Real-time PCR. Peripheral blood-derived macrophages (PBMs) were cultured in vitro and induced into M1 and M2 macrophages by LPS and IL-4, respectively. After intervention with JWH133, the polarity of macrophages was measured by Real-time PCR. Results: There were a large number of macrophages in the colonic tissues of UC patients. JWH133 transformed the polarity of macrophages from M1 to M2 in UC mice, improved the weight loss and DAI of mice, and significantly decreased the degree of intestinal inflammation. In vitro, JWH133 decreased the level of M1-PBM markers (TNF-α, IL-1β and IL-12) and elevated Arg1, Mrc2 and Mgl1 of M2-PBM. Conclusion:CB2 receptor can improve UC by regulating macrophage transformation to M2 type.