Arachidonic Acid Metabolism Controls Macrophage Alternative Activation Through Regulating Oxidative Phosphorylation in PPARγ Dependent Manner

• DOI: 10.3389/fimmu.2021.618501
• Publication Date: 2021-06-03T23:51:16Z
• Authors: Miao Xu; Xiaohong Wang; Yongning Li; Xue Geng; Xudong Jia; Lishi Zhang; Hui Yang
• Keywords: Macrophage polarization

Macrophage polarization is mainly steered by metabolic reprogramming in the tissue microenvironment, thus leading to distinct outcomes of various diseases. However, role lipid metabolism regulation macrophage alternative activation incompletely understood. Using human THP-1 and mouse bone marrow derived models, we revealed a pivotal for arachidonic acid determining phenotype M2 macrophages. We demonstrated that was inhibited acid, but inversely facilitated its metabolite prostaglandin E2 (PGE2). Furthermore, PPARγ bridges these two seemingly unrelated processes via modulating oxidative phosphorylation (OXPHOS). Through inhibiting PPARγ, PGE2 enhanced OXPHOS, resulting macrophages, which counterweighted PPARγ. This connection between biosynthesis also existed esophageal squamous cell carcinoma. Our results highlight critical as immune regulators homeostasis pathological process.