Wang Wei, Xu Rong-Li, He Ping, Chen Rui
Department of Emergency, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No.19, Xiuhua Road, 570311, Haikou, Hainan Province, People's Republic of China.
Department of Cardiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No.19, Xiuhua Road, 570311, Haikou, Hainan Province, People's Republic of China.
J Inflamm (Lond). 2021 Feb 8;18(1):8. doi: 10.1186/s12950-021-00271-x.
Sepsis is a complex syndrome characterized by a dysregulated inflammatory response to systemic infection and leads to shock, multiple organ failure and death especially if not recognized early and treated promptly. Previous studies have suggested Maresin 1 (MAR1) can alleviate systemic inflammation in sepsis, but its mechanism has not been clarified.
RAW 264.7 cells and human primary peripheral blood mononuclear cells (hPBMCs) were pretreated with LPS and MAR1. The mRNA expression and supernatant levels of pro-inflammatory cytokines, tumor necrosis factor (TNF-α), interleukin (IL)-1β and IL-6 were evaluated by RT-qPCR and ELISA, respectively. The expression levels of Sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and Peroxisome proliferator-activated receptor gamma (PPAR-γ) were determined by RT-qPCR and Western blot analysis, respectively.
Our results show that LPS-induced inflammation increased the expression and secretion of proinflammatory cytokines TNF-α, IL-1β and IL-6 and induced suppression of SIRT1, PGC-1α, and PPAR-γ expression, which could be reversed by MAR1. And the effect of MAR1 was eliminated by repression of SIRT1/PPAR-γ and enhanced by PGC-1α overexpression.
MAR1 suppressed inflammatory response in LPS-induced RAW 264.7 macrophages and hPBMCs via the SIRT1/PGC-1α/PPAR-γ pathway.
脓毒症是一种复杂的综合征,其特征为对全身感染的炎症反应失调,若不及早识别和及时治疗,会导致休克、多器官功能衰竭甚至死亡。既往研究提示maresin 1(MAR1)可减轻脓毒症中的全身炎症,但具体机制尚未阐明。
用脂多糖(LPS)和MAR1预处理RAW 264.7细胞和人原代外周血单核细胞(hPBMCs)。分别通过逆转录定量聚合酶链反应(RT-qPCR)和酶联免疫吸附测定(ELISA)评估促炎细胞因子肿瘤坏死因子(TNF-α)、白细胞介素(IL)-1β和IL-6的mRNA表达及上清液水平。分别通过RT-qPCR和蛋白质免疫印迹分析测定沉默调节蛋白1(SIRT1)、过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)和过氧化物酶体增殖物激活受体γ(PPAR-γ)的表达水平。
我们的结果显示,LPS诱导的炎症增加了促炎细胞因子TNF-α、IL-1β和IL-6的表达与分泌,并诱导了SIRT1、PGC-1α和PPAR-γ表达的抑制,而MAR1可使其逆转。并且,抑制SIRT1/PPAR-γ可消除MAR1的作用,而过表达PGC-1α可增强其作用。
MAR1通过SIRT1/PGC-1α/PPAR-γ途径抑制LPS诱导的RAW 264.7巨噬细胞和hPBMCs中的炎症反应。