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


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 AMPK?1 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-?B 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-?B pathway.

SUBMITTER: Kumase F 

PROVIDER: S-EPMC4723067 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Kumase Fumiaki F   Takeuchi Kimio K   Morizane Yuki Y   Suzuki Jun J   Matsumoto Hidetaka H   Kataoka Keiko K   Al-Moujahed Ahmad A   Maidana Daniel E DE   Miller Joan W JW   Vavvas Demetrios G DG  

PloS one 20160122 1


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  ...[more]

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