title: Retinoid acid receptor-related orphan receptor alpha (RORα) regulates macrophage M2 polarization via activation of AMPKα.
abstract: Macrophages are able to polarize to pro-inflammatory M1 or anti-inflammatory M2 states with distinct phenotypes and physiological functions. RORα is a member of the nuclear receptor super family and plays important roles in lipid, glucose metabolism, as well as the inflammatory response. In this study, we examined the potential function of RORα in the regulation of macrophage polarization. Treatment of RAW264.7 macrophages with RORα agonist cholesterol sulfate (CH-S) and overexpression of RORα increased M2 macrophage markers expressions (Arg1, Ym1 and Fizz1) both on mRNA and protein levels. Conversely, selective antagonism (SR1001) abrogated the induction of M2 macrophage markers which induced by CH-S. In addition, CH-S induced phosphorylation of Adenosine monophosphate (AMP)-activated protein kinase α (AMPKα), which was accompanied by the activation of acetyl-CoA carboxylase 1 (ACC). However, SR1001 abolished the activation of AMPKα and ACC induced by CH-S. Meanwhile, inactivation of AMPKα by its inhibitor Compound C (CompC) abrogated the mRNA and protein levels of CH-S-induced M2 macrophage markers expressions. Together these findings reveal that RORα regulates macrophage M2 polarization via activation of AMPKα, which may provide a novel beneficial effect of RORα against inflammation.
authors: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors: Lei
authors: L
authors: Xiao
authors: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors: Zihui
authors: Z
authors: Zhang
authors: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors: Xiaoqin
authors: X
authors: Luo
authors: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors: Haixia
authors: H
authors: Yang
authors: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors: Fan
authors: F
authors: Li
authors: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China; The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China. Electronic address: nanpingwang2003@yahoo.com.
authors: Nanping
authors: N
authors: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D005434:Flow Cytometry; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000276:immunology* / Q000378:metabolism; D000067996:RAW 264.7 Cells
chemical_list: D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539739:Rora protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: AMPKα; M2 macrophage; Polarization; RORα