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Journal of Surgical Research

Journal of Surgical Research

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Maresin1 Promotes M2 Macrophage Polarization Through Peroxisome Proliferator–Activated Receptor-γ Activation to Expedite Resolution of Acute Lung Injury

Published:1 December 2020 DOI: 10.1016/j.jss.2020.06.062 PMID: 32805581
Nan Qiao MD , Yun Lin PhD , Zhe Wang PhD , Jia-Yi Chen MD , Yang-Yang Ge MD , Shang-Long Yao PhD , Jie Gong PhD

Abstract

Background

Acute lung injury (ALI), manifested by progressive hypoxemia and respiratory distress, is associated with high morbidity and mortality, which lacks the effective therapies in clinics. Our previous studies demonstrated that maresin1 (MaR1), a specialized proresolving mediator, could effectively mitigate the inflammation of lipopolysaccharide (LPS)-induced ALI. However, whether MaR1 impacts the macrophage polarization to alleviate ALI remains unclear. Our study explored the effects and underlying mechanisms of MaR1 on the macrophage phenotypes in ALI.

Material and methods

Male BALB/c mice were subjected to endotracheal instillation of LPS to induce ALI and then intravenously injected with MaR1 or normal saline. Intraperitoneal administration of peroxisome proliferator–activated receptor-γ (PPAR-γ) inhibitor GW9662 was given 30?mins before MaR1. We measured the pathohistologic changes, pulmonary edema, inflammatory cytokines, and the flow cytometry of macrophage phenotypes.

Results

Our results illustrated that MaR1 ameliorated lung injury and increased monocyte or macrophage recruitment and the release of anti-inflammatory cytokines. The flow cytometry showed that MaR1 promoted polarization of CD11c?CD206+ (M2) macrophages and inhibited polarization of CD11c+CD206- (M1) macrophages. Besides, the western blotting revealed that MaR1 increased the expression of PPAR-γ. The pretreatment with PPAR-γ antagonist GW9662 could significantly suppress the polarization of M2 macrophages and antagonize the protective effects of MaR1 on LPS-stimulated ALI.

Conclusions

MaR1 was able to promote M2 macrophage polarization by reversing LPS-mediated PPAR-γ inhibition, thereby expediting the recovery of LPS-stimulated ALI.

Substances (5)

Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
GW9662 22978-25-2 C13H9ClN2O3 299 suppliers $5.00-$1593.90
GW9662 22978-25-2 C13H9ClN2O3 299 suppliers $5.00-$1593.90
GW9662 22978-25-2 C13H9ClN2O3 299 suppliers $5.00-$1593.90
GW9662 22978-25-2 C13H9ClN2O3 299 suppliers $5.00-$1593.90

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