AMPK-Activated Protein Kinase Suppresses Ccr2 Expression by Inhibiting the NF-kappa B Pathway in RAW264.7 Macrophages

作者：Kumase Fumiaki; Takeuchi Kimio; Morizane Yuki; Suzuki Jun; Matsumoto Hidetaka; Kataoka Keiko; Al Moujahed Ahmad; Maidana Daniel E; Miller Joan W; Vavvas Demetrios G^*

来源：PLos One, 2016, 11(1): e0147279.

DOI：10.1371/journal.pone.0147279

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 AMPKa1 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-kappa B inhibition whereas TNF-alpha 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-kappa B pathway.

• 出版日期2016-1-22