AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced murine acute and relapsing colitis

摘要: AMP-activated protein kinase (AMPK), a cellular energy sensor, has been reported to participate in modulating inflammatory responses, but its role intestinal inflammation remains unclear. IBD characterized by excessive innate and adaptive immune responses. Here, the roles of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an agonist AMPK, regulating responses experimental colitis were investigated. In vitro effects AICAR on LPS-induced macrophage activation Th1 Th17 differentiation, as well vivo mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, explored. acute daily treatment commenced 2 days after TNBS delivery (day 1), while relapsing three weekly administrations. Colon inflammation, production proinflammatory cytokines NF-κB colon tissues, cell populations lamina propria mononuclear cells (LPMCs) mesenteric lymph node (MLNs) assayed. Results show that significantly inhibited differentiation. Administration was therapeutically effective ameliorating shown reduced body weight loss significant attenuation histological inflammation. Moreover, this macrophages, levels TNF, Th1- Th17-type cytokines, LPMCs MLNs. AICAR-initiated AMPK may act central downregulator ongoing murine providing novel therapeutic approach IBD.