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.

中文翻译：

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MAR1通过SIRT1 /PGC-1α/PPAR-γ途径抑制LPS诱导的RAW 264.7巨噬细胞和人原代外周血单个核细胞的炎症反应

败血症是一种复杂的综合征，其特征在于对全身感染的炎症反应失调，并导致休克，多器官功能衰竭和死亡，尤其是如果不能及早发现并及时治疗。先前的研究表明，Maresin 1（MAR1）可以减轻败血症的全身性炎症，但其机制尚未阐明。用LPS和MAR1预处理RAW 264.7细胞和人原代外周血单个核细胞（hPBMC）。通过RT-qPCR和ELISA分别评估促炎细胞因子，肿瘤坏死因子（TNF-α），白介素（IL）-1β和IL-6的mRNA表达和上清水平。Sirtuin 1（SIRT1），过氧化物酶体增殖物激活的受体γcoactivator-1α（PGC-1α）的表达水平，通过RT-qPCR和Western blot分析分别测定PPAR-γ和过氧化物酶体增殖物激活的受体γ（PPAR-γ）。我们的结果表明，LPS诱导的炎症会增加促炎细胞因子TNF-α，IL-1β和IL-6的表达和分泌，并诱导抑制SIRT1，PGC-1α和PPAR-γ的表达，这可能被MAR1逆转。通过抑制SIRT1 /PPAR-γ消除了MAR1的作用，并通过PGC-1α的过表达增强了MAR1的作用。MAR1通过SIRT1 /PGC-1α/PPAR-γ途径抑制LPS诱导的RAW 264.7巨噬细胞和hPBMC中的炎症反应。MAR1可以逆转。通过抑制SIRT1 /PPAR-γ消除了MAR1的作用，并通过PGC-1α的过表达增强了MAR1的作用。MAR1通过SIRT1 /PGC-1α/PPAR-γ途径抑制LPS诱导的RAW 264.7巨噬细胞和hPBMC中的炎症反应。MAR1可以逆转。通过抑制SIRT1 /PPAR-γ消除了MAR1的作用，并通过PGC-1α的过表达增强了MAR1的作用。MAR1通过SIRT1 /PGC-1α/PPAR-γ途径抑制LPS诱导的RAW 264.7巨噬细胞和hPBMC中的炎症反应。