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 language | English |
|---|---|
| Article number | e0147279 |
| Journal | PLoS One |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2016 |
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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 journal › Article
}
TY - JOUR
T1 - AMPK-activated protein kinase suppresses Ccr2 expression by inhibiting the NF-κB pathway in RAW264.7 macrophages
AU - Kumase, Fumiaki
AU - Takeuchi, Kimio
AU - Morizane, Yuki
AU - Suzuki, Jun
AU - Matsumoto, Hidetaka
AU - Kataoka, Keiko
AU - Al-Moujahed, Ahmad
AU - Maidana, Daniel E.
AU - Miller, Joan W.
AU - Vavvas, Demetrios G.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84958214211&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0147279
DO - 10.1371/journal.pone.0147279
M3 - Article
C2 - 26799633
AN - SCOPUS:84958214211
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 1
M1 - e0147279
ER -