Open AccessAMPK-Activated Protein Kinase Suppresses Ccr2 Expression by Inhibiting the NF-κB Pathway in RAW264.7 Macrophages
Author(s) -
Fumiaki Kumase,
K. Takeuchi,
Yuki Morizane,
Jun Suzuki,
Hidetaka Matsumoto,
Keiko Kataoka,
Ahmad Al-Moujahed,
Daniel E. Maidana,
Joan W. Miller,
Demetrios G. Vavvas
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0147279
Subject(s) - ampk , ccr2 , protein kinase a , amp activated protein kinase , microbiology and biotechnology , chemistry , downregulation and upregulation , regulator of g protein signaling , regulator , signal transduction , gene knockdown , p38 mitogen activated protein kinases , nf κb , kinase , chemokine , chemokine receptor , biology , receptor , g protein , biochemistry , gene , apoptosis , gtpase activating protein
C-C chemokine receptor 2 (Ccr2) is a key pro-inflammatory marker of classic (M1) macrophage activation. Although Ccr2 is known to be expressed both constitutively and inductively, the full regulatory mechanism of its expression remains unclear. AMP-activated protein kinase (AMPK) is not only a master regulator of energy homeostasis but also a central regulator of inflammation. In this study, we sought to assess AMPK’s role in regulating RAW264.7 macrophage Ccr2 protein levels in resting (M0) or LPS-induced M1 states. In both M0 and M1 RAW264.7 macrophages, knockdown of the AMPKα1 subunit by siRNA led to increased Ccr2 levels whereas pharmacologic (A769662) activation of AMPK, attenuated LPS-induced increases in Ccr2 expression in an AMPK dependent fashion. The increases in Ccr2 levels by AMPK downregulation were partially reversed by NF-κB inhibition whereas TNF-a inhibition had minimal effects. Our results indicate that AMPK is a negative regulator of Ccr2 expression in RAW264.7 macrophages, and that the mechanism of action of AMPK inhibition of Ccr2 is mediated, in part, through the NF-κB pathway.