Dataset Information

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

ACCESS DATA

Publications

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]

PMID: 26799633

Similar Datasets

Project description:Colorectal cancer (CRC) is one of the leading causes of cancer?associated mortality. Asiaticoside (AC) exhibits antitumor effects; however, to the best of our knowledge, the biological function of AC in CRC cells remains unclear. Therefore, the aim of the present study was to investigate the effect of AC on CRC cells. In the present study, CCK?8 and colony formation assays were performed to assess the effects of AV on human CRC cell lines (HCT116, SW480 and LoVo). Mitochondrial membrane potential was examined by JC?1 staining. Cell apoptosis and cell cycle were monitored by flow cytometry, and the expression of genes was evaluated using RT?qPCR and western blot analysis. Furthermore, the biological effect of AC in vivo was detected using a xenograft mouse model. The findings revealed that 2 µM AC suppressed the proliferation of CRC cells in a time? and dose?dependent manner, but had no adverse effects on normal human intestinal FHC cells at a range of concentrations. AC decreased the mitochondrial membrane potential and increased the apoptosis of CRC cells in a dose?dependent manner. Furthermore, AC induced cell cycle arrest at the G0/G1 phase. AC attenuated I?B? phosphorylation in a dose?dependent manner, thereby preventing P65 from entering the nucleus, and resulting in inhibition of the NF??B signaling pathway. In addition, AC significantly reduced the expression of CDK4 and Cyclin D1 in a dose?dependent manner, significantly upregulated the activation of caspase?9 and caspase?3, and decreased the Bcl?2/Bax mRNA ratio. Furthermore, treatment with the NF??B signaling pathway inhibitor JSH?23 significantly increased the cytotoxicity of AC in CRC cells. Findings of the xenograft mice model experiments revealed that AC significantly inhibited colorectal tumor growth in a dose?dependent manner. Overall, AC suppressed activation of the NF??B signaling pathway by downregulating I?B? phosphorylation. This resulted in inhibition of CRC cell viability and an increase of cell apoptosis, which may form the basis of AC use in the treatment of patients with CRC.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure