Role of Rac1 signaling pathway of azathioprine and peptidoglycan in the regulation of monocyte-macrophage apoptosis in Crohn's disease / 中华内科杂志

ABSTRACT

Objective To evaluate the changes of macrophages and expression of Rac1 in the inflammatory site of Crohn's disease,and to investigate the effects of 6-thioguanine (6-TG) and peptidoglycan on apoptosis of human peripheral blood monocyte-macrophage by regulating Rac1 signaling pathway.Methods Ten patients with Crohn's disease and eight healthy controls diagnosed were enrolled at Department of Gastroenterology and Hepatology,Tianjin Medical University General Hospital from January 2013 to January 2014.The number of macrophages,apoptosis and expression of Rac1 in the inflammation sites and non-inflammation sites of intestinal mucosa were detected in both patients and controls.Peripheral blood mononuclear cells (PBMCs) were sorted by CD14 immunomagnetic beads.The apoptosis of monocytes,expression of Rac1 and related apoptosis signaling molecules were detected in patients treated with peptidoglycan,6-TG and Rac1 inhibitor NSC23766 and another 15 healthy donors.Results The number of macrophages and apoptotic cells significantly increased in the inflammatory group of Crohn's disease patients compared with the non-inflammatory group.The expression of PAK1,downstream molecular of Rac1 signaling pathway of macrophages was also significantly higher in the inflammatory group of Crohn's disease patients than that in healthy controls and non-inflammatory group.Compared with control group,anti-apoptotic signals (NF-κB,Bcl-xL and STAT-3) in PBMCs increased in the peptidoglycan group,while slightly decreased in 6-TG group.6-TG and NSC23766 significantly promoted peptidoglycan-related anti-apoptosis [peptidoglycan group (8.6±3.7)％,peptidoglycan + 6-TG group (42.0±2.7)％,peptidoglycan + NSC23766 group (58.5±6.9)％,P＜0.05].Conclusions Peptidoglycan plays a role in the pathogenesis of Crohn's disease by recruiting macrophages.However,6-TG inhibits peptidoglycan-induced activation of Rac 1 signaling pathway leading to macrophage apoptosis.