April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
AMP-activated Protein Kinase Suppresses CCR2 Expression by Inhibiting the NF-κB Pathway in Macrophages
Author Affiliations & Notes
  • Fumiaki Kumase
    Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Kimio Takeuchi
    Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Yuki Morizane
    Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
    Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Jun Suzuki
    Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
    Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
  • Keiko Kataoka
    Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Hidetaka Matsumoto
    Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Joan W Miller
    Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
  • Demetrios G Vavvas
    Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1873. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Fumiaki Kumase, Kimio Takeuchi, Yuki Morizane, Jun Suzuki, Keiko Kataoka, Hidetaka Matsumoto, Joan W Miller, Demetrios G Vavvas; AMP-activated Protein Kinase Suppresses CCR2 Expression by Inhibiting the NF-κB Pathway in Macrophages. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1873.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: The CC chemokine receptor 2 (CCR2) is one of the pro-inflammatory M1 macrophage markers. Although CCR2 is known to express both inductively and constitutively, the regulatory mechanism of the expression remains unclear. In this study, we focused on the constitutive expression of CCR2 and AMP-activated kinase (AMPK), a central regulator of energy homeostasis, and investigated the role of AMPK on constitutive expression of CCR2 in macrophages.

Methods: We used macrophage cell line, RAW264.7. We activated or inhibited the kinase activity of AMPK by treating cells with AMPK specific activator A769662 or by knocking down AMPKα1 subunit with siRNA method, respectively. The effects of the change in AMPK activity on constitutive CCR2 expression were examined by flow cytometry. To determine the involvement of NF-κB pathway in the constitutive expression of CCR2, we used selective NF-κB inhibitors of BMS345541 and SM7368 and examined the CCR2 expression by flow cytometry.

Results: Activation of AMPK with A769662 decreased the percentage of CCR2-positive cells significantly (P < 0.05). Conversely, the knockdown of AMPKα1 subunit increased the percentage of CCR2-positive cells significantly (P < 0.05). The knockdown of AMPKα1 subunit resulted in the activation of NF-κB pathway. Consistently, both BMS345541 and SM7368 inhibited the increasing effect of AMPKα1 knockdown on the percentage of CCR2-positive cells (P < 0.05).

Conclusions: Our results indicate that the activation of AMPK suppresses constitutive CCR2 expression in RAW264.7 cells by inhibiting the NF-κB pathway. AMPK activation may be involved in the M1 to M2 macrophage switch.

Keywords: 674 receptors • 714 signal transduction • 557 inflammation  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×