The Study Of The Role Of Neutrophil In The Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease(NAFLD)is a spectrum of liver disease characterized by the presence of ectopic fat steatosis and in the liver which cannot be explained by alcohol consumption.There were approximately 1 billion NAFLD patients all around the world and about 300 million NAFLD patients in China according to the statistic data of WHO.NAFLD is unanimously considered to be blamed for being one of the leading causes of liver cirrhosis and liver cancer and for deteriorating the condition of patients which suffer from atherosclerosis and hypertension.Thus,NAFLD is now a real threat to the health of human being.NAFLD will cause damage of the hepatocytes,and damaged hepatocytes will release damage-associated molecular patterns such as histone and HGMB1 which can be recognized by the immune system and finally lead to inflammation.We observed increased expressions of IL-1?,IL-6and TNF-? accompanied by enhanced numbers and rates of neutrophils in peripheral blood.NAFLD mice model was obtained and significant higher numbers and rates of neutrophils in peripheral blood were observed in NAFLD model mice.Ther were also higher NETs and hepatocytes apoptosis in NAFLD model mice,while NETs and hepatocytes apoptosis were down-regulated when treated with MPO-DNA inhibitor or/and citrullinated-histone H3 inhibitor.There were higher expressions of IL-1?,IL-6and TNF-? in Kuffer cells when Kuffer cells were co-cultured with activated neutrophils.NAFLD model mice were injected with anti-Ly6 G antibody and then the neutrophils were depleted,TLR4 KO,TLR9KO or TLR4/9KO neutrophils were adoptive transferred to the NAFLD model mice 24 hours after neutrophils depletion.Then NETs and hepatocytes apoptosis are significant lower,and there were decreased expressions of TNF-? in Kuffer cells too.Our research is abundant to explain that damaged hepatocytes can release DAMPs and activate neutrophils through TLR4 and TLR9 signal pathway,then more NETs are formed and lead to higher hepatocyte apoptosis,activated neutrophils can also promote the IL-1?,IL-6 and TNF-? production of Kuffer cells which finally aggravate the damage of hepatocytes.