NLRP6 exerts a protective role via NF-kB with involvement of CCL20 in a mouse model of alcoholic hepatitis

Alcoholic hepatitis (AH) is an important form of alcoholic liver disease (ALD), and its incidence is continuously increasing leading to advanced disease burden. The NOD-like receptors (NLRs) are a specialized group of intracellular pattern recognition receptors, which participate in inflammatory diseases. However, the role of NLRs in the pathogenesis of AH still remain obscure. The animal model of alcoholic hepatitis in mice was established according to National Institute on Alcohol Abuse and Alcoholism (NIAAA) method. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of NLR family members in liver tissues of the ethanol-fed(EtOH-fed)group and pair-fed group. NLRP6 was overexpressed in mice by injecting Recombinant Adeno-Associated Virus into the tail vein. Mouse Cytokines and Chemokines RT2 Profiler PCR Array was used to analyze the related cytokines and chemokines involved in the development of alcoholic hepatitis. Among the NLR family members, the expression of NLRP6 decreased most significantly in the animal model of AH. Our results demonstrated that overexpression of NLRP6 in vivo obviously alleviated steatosis, inflammation and fibrosis in liver. Meanwhile, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice also decreased. Besides, Chemokine (CeC motif) ligand 20(CCL20) was one of the most significantly up-regulated chemokines in the mouse AH model and CCL20 was participated in NLRP6-mediated AH. NLRP6 could inhibit the activation of nuclear factor (NF)-kappa B signaling pathway in vitro and in vivo. Furthermore, the activation, proliferation, and migration of hepatic stellate cells was enhanced after downregulation of NLRP6. In summary, NLRP6 may play a protective role in the development of AH. NLRP6 could inhibit activation of NF-kappa B signaling pathway in AH. (C) 2020 The Authors. Published by Elsevier Inc.