AMPK-activated protein kinase suppresses Ccr2 expression by inhibiting the NF-κB pathway in RAW264.7 macrophages

Fumiaki Kumase, Kimio Takeuchi, Yuki Morizane, Jun Suzuki, Hidetaka Matsumoto, Keiko Kataoka, Ahmad Al-Moujahed, Daniel E. Maidana, Joan W. Miller, Demetrios G. Vavvas

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14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0147279
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kumase, F., Takeuchi, K., Morizane, Y., Suzuki, J., Matsumoto, H., Kataoka, K., Al-Moujahed, A., Maidana, D. E., Miller, J. W., & Vavvas, D. G. (2016). AMPK-activated protein kinase suppresses Ccr2 expression by inhibiting the NF-κB pathway in RAW264.7 macrophages. PloS one, 11(1), [e0147279]. https://doi.org/10.1371/journal.pone.0147279