1. Academic Validation
  2. MAR1 suppresses inflammatory response in LPS-induced RAW 264.7 macrophages and human primary peripheral blood mononuclear cells via the SIRT1/PGC-1α/PPAR-γ pathway

MAR1 suppresses inflammatory response in LPS-induced RAW 264.7 macrophages and human primary peripheral blood mononuclear cells via the SIRT1/PGC-1α/PPAR-γ pathway

  • J Inflamm (Lond). 2021 Feb 8;18(1):8. doi: 10.1186/s12950-021-00271-x.
Wei Wang  # 1 Rong-Li Xu  # 2 Ping He 3 Rui Chen 4
Affiliations

Affiliations

  • 1 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. ww_smile@qq.com.
  • 2 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.
  • 3 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.
  • 4 Department of Medical Intensive Care Unit, General Hospital of Southern Theater Command, PLA, No.111, Liuhua Road, 510010, Guangzhou, People's Republic of China. crui_rui@126.com.
  • # Contributed equally.
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: MAR1 suppressed inflammatory response in LPS-induced RAW 264.7 macrophages and hPBMCs via the SIRT1/PGC-1α/PPAR-γ pathway.

Keywords

MAR1; PGC-1α; PPAR-γ; SIRT1; Sepsis.

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