Regulation Mechanism Of Myeloid ATF3 On Immune Activation Response To Liver Ischemia Reperfusion Injure

Objective: To investigate the regulation mechanism of myeloid ATF3 on immune activation response to liver ischemia reperfusion injury in mice.Methods: Using mice liver ischemia reperfusion injury model to analyze the liver damage and the recruitment of macrophages in ATF3 knockout mice,including serum ALT,HE,Ly6 G,CD11b and TUNEL staining.Real-time quantitative PCR technique was used to detect the conditions of cytokine production in the liver and cells.The indexes were TNF-a,IL-1,IL-6,and TGF-?.The expression of m TOR,HIF-1?,p70S6 K,TLR4 and PHD1 in tissues and cells were detected by Weatern Blot.The immunomodulatory function was verified by inhibiting the m TOR activation,and the the p70S6 K si RNA transfection test was used to verify its role in the m TOR signaling pathway,and the function of the inflammatory immune regulation mediated by ATF3 was verified by the HIF-1a si RNA inhibition test.Results: Compared with the control group,ATF3 knockout significantly aggravated liver injury induced by ischemia-reperfusion.ATF3 knockout promoted macrophage / neutrophil invasion and hepatocyte apoptosis.ATF3 knockout promoted the expression of m TOR,p70S6 K,TLR4 and HIF-1a,but reduced the expression of PHD1.The results of m TOR targeting inhibition test,p70S6 K si RNA inhibition test and HIF-1a si RNA inhibition test showed that the liver injury induced by ATF3 knockout was obviously reversed,the expression of inflammatory cytokines TNF-a,IL-1,IL-6 expression decreased,and the expression of TGFincreased.Liver cell apoptosis and liver function also improved significantly.Conclusions: ATF3 in myeloid cells downregulates m TOR/p70S6K/HIF-1? signaling pathway to control immune activation against liver ischemia reperfusion injury.