The effect of adiponectin on LPS-induced inflammation via autophagy in RAW 264.7 macrophages:

European Journal of Inflammation

XiaoliangWang¹ 

关键词: adiponectin;    anti-inflammatory;    autophagy;    RAW264.7;    sepsis;   

DOI  :  10.1177/1721727X17737208

学科分类：医学（综合）

来源: Sage Journals

【 摘 要 】

Mitochondrial dysfunction is involved in the process of sepsis and leads to the accumulation of reactive oxygen species (ROS), which breaks cellular homeostasis and activates the downstream inflammatory cascade. The autophagic removal of ROS is a well-established cellular adaptive mechanism. Adiponectin is an adipocytokine that plays an important role in metabolic and inflammatory regulation. In this study, we investigated the anti-inflammatory effect of adiponectin in a sepsis model and its potential association with autophagy. We induced RAW 264.7 macrophages with lipopolysaccharide (LPS) to set up the sepsis model and treated them with adiponectin, an inhibitor of the nucleotide-binding domain and leucine-rich repeat containing family pyrin domain–containing 3 (NLRP3), ROS, Complex I, and an autophagy inhibitor. Flow cytometry and western blot analysis were performed to detect the expression levels of ROS, NLRP3, interleukin-1 beta (IL-1β), microtubule-associated protein 1A/1B-light chain 3II/I (LC3II/I), and adenosine monophosphate–activated protein kinase (AMPK). Expression levels of NLRP3, IL-1β, and ROS were significantly increased following LPS induction, and adiponectin reversed this up-regulation. Meanwhile, adiponectin also enhanced the expression of LC3II/I, an autophagosome marker, but an autophagy inhibitor and AMPK inhibitor depleted (reversed) the anti-inflammatory and antioxidant effect of adiponectin. Taken together, in the LPS-induced sepsis model, adiponectin alleviated the inflammatory reaction by reducing ROS production, possibly by enhancing autophagy via the AMPK pathway. The activation of autophagy may therefore be a key mechanism by which adiponectin ameliorates the inflammatory reactions of sepsis.

【 授权许可】

CC BY-NC