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

Research output: Contribution to journalArticle

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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

Fingerprint

AMP-activated protein kinase
CC Chemokines
AMP-Activated Protein Kinases
Macrophages
Chemokine Receptors
protein kinase C
Protein Kinase C
macrophages
A 769662
Chemical activation
macrophage activation
Macrophage Activation
beta chemokines
chemokine receptors
small interfering RNA
Small Interfering RNA
mechanism of action
homeostasis
Homeostasis
Down-Regulation

ASJC Scopus subject areas

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

Cite this

AMPK-activated protein kinase suppresses Ccr2 expression by inhibiting the NF-κB pathway in RAW264.7 macrophages. / Kumase, Fumiaki; Takeuchi, Kimio; Morizane, Yuki; Suzuki, Jun; Matsumoto, Hidetaka; Kataoka, Keiko; Al-Moujahed, Ahmad; Maidana, Daniel E.; Miller, Joan W.; Vavvas, Demetrios G.

In: PLoS One, Vol. 11, No. 1, e0147279, 01.01.2016.

Research output: Contribution to journalArticle

Kumase, F, Takeuchi, K, Morizane, Y, Suzuki, J, Matsumoto, H, Kataoka, K, Al-Moujahed, A, Maidana, DE, Miller, JW & Vavvas, DG 2016, 'AMPK-activated protein kinase suppresses Ccr2 expression by inhibiting the NF-κB pathway in RAW264.7 macrophages', PLoS One, vol. 11, no. 1, e0147279. https://doi.org/10.1371/journal.pone.0147279
Kumase, Fumiaki ; Takeuchi, Kimio ; Morizane, Yuki ; Suzuki, Jun ; Matsumoto, Hidetaka ; Kataoka, Keiko ; Al-Moujahed, Ahmad ; Maidana, Daniel E. ; Miller, Joan W. ; Vavvas, Demetrios G. / AMPK-activated protein kinase suppresses Ccr2 expression by inhibiting the NF-κB pathway in RAW264.7 macrophages. In: PLoS One. 2016 ; Vol. 11, No. 1.
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