1. Academic Validation
  2. Anti-inflammatory activities of fenoterol through β-arrestin-2 and inhibition of AMPK and NF-κB activation in AICAR-induced THP-1 cells

Anti-inflammatory activities of fenoterol through β-arrestin-2 and inhibition of AMPK and NF-κB activation in AICAR-induced THP-1 cells

  • Biomed Pharmacother. 2016 Dec;84:185-190. doi: 10.1016/j.biopha.2016.09.044.
Wei Wang 1 Jing Chen 1 Xiao Guang Li 1 Jie Xu 2
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, Peking University Third Hospital, Hua-Yuan North Road 49, Haidian District, Beijing 100191, China.
  • 2 Department of Infectious Diseases, Peking University Third Hospital, Hua-Yuan North Road 49, Haidian District, Beijing 100191, China. Electronic address: xujie1998@126.com.
Abstract

The AMP-activated protein kinase (AMPK) pathway has been shown to be able to regulate inflammation in several cell lines. We reported that fenoterol, a β2-adrenergic receptor (β2-AR) agonist, inhibited lipopolysaccharide (LPS)-induced AMPK activation and inflammatory cytokine production in THP-1 cells, a monocytic cell line in previous studies. 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (AICAR) is an agonist of AMPK. Whether AICAR induced AMPK activation and inflammatory cytokine production in THP-1 cells can be inhibited by fenoterol is unknown. In this study, we explored the mechanism of β2-AR stimulation with fenoterol in AICAR-induced inflammatory cytokine secretion in THP-1 cells. We studied AMPK activation using p-AMPK and AMPK Antibodies, nuclear factor-kappa B (NF-κB) activation and inflammatory cytokine secretion in THP-1 cells stimulated by β2-AR in the presence or absence of AICAR and small interfering RNA (siRNA)-mediated knockdown of β-arrestin-2 or AMPKα1 subunit. AICAR-induced AMPK activation, NF-κB activation and tumor necrosis factor (TNF)-α release were reduced by fenoterol. In addition, siRNA-mediated knockdown of β-arrestin-2 abolished fenoterol's inhibition of AICAR-induced AMPK activation and TNF-α release, thus β-arrestin-2 mediated the anti-inflammatory effects of fenoterol in AICAR-treated THP-1 cells. Furthermore, siRNA-mediated knockdown of AMPKα1 significantly attenuated AICAR-induced NF-κB activation and TNF-α release, so AMPKα1 was a key signaling molecule involved in AICAR-induced inflammatory cytokine production. These data suggested that fenoterol inhibited AICAR-induced AMPK activation and TNF-α release through β-arrestin-2 in THP-1 cells. Management especially inhibition of AMPK signaling may provide new approaches and strategies for the treatments of immune diseases including inflammatory diseases and other critical illness.

Keywords

AICAR; AMPK; Fenoterol; β(2)-adrenoceptor; β-arrestin-2.

Figures
Products