β2AR介导的巨噬细胞焦亡在精神应激诱发小鼠十二指肠炎症中的作用OA

Objective To investigate whether psychological stress causes duodenal inflammation and the related molecular mechanisms.Methods This study employed a chronic restraint stress(CRS)mouse model,which was supplemented with in vitro models using RAW264.7 and THP-1 monocytic/macrophage cell lines.Techniques including RT-qPCR,Western blot,HE staining,and immunohistochemistry were used to investigate the expression alterations of inflammatory cytokines,pyroptosis pathway-related proteins,and hormone receptors.Results CRS significantly triggered an inflammatory response in the duodenal tissue of mice,which was characterized by heightened levels of inflammatory cytokines such as IL-1β,IL-18,and TNF-α,along with elevated histological scores(P＜0.05).This pro-inflammatory effect was mediated by the β2-adrenergic receptor(β2AR),rather than the glucocorticoid receptor.Further research demonstrated that CRS facilitated the proliferation of macrophages in the duodenal mucosa,and the chemical depletion of macrophages effectively inhibited CRS-induced inflammation(P＜0.01).Mechanistically,CRS activated the classical NLRP3/Caspase1/GSDMD-mediated pyroptosis pathway in duodenal macrophages,as indicated by the increased protein level of the activated N-terminal fragment of GSDMD.In vitro experiments verified that the stress hormone epinephrine could directly activate the macrophage pyroptosis pathway and stimulate the release of inflammatory cytokines via β2AR(P＜0.05).Conclusions Psychological stress triggers the activation of the sympathetic-adrenal medulla system.This activation promotes GSDMD-mediated pyroptosis in duodenal macrophages through the β2AR signaling pathway,ultimately resulting in duodenal mucosal inflammation.