Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, Epiciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

AMPK Activation by A-769662 Controls IL-6 Expression in Inflammatory Arthritis

Abstract : AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase critically involved in the regulation of cellular energy homeostasis. It is a central regulator of both lipid and glucose metabolism. Many studies have suggested that AMPK activation exert significant anti-inflammatory and immunosuppressive effects. In this study, we assessed whether targeted activation of AMPK inhibits inflammatory arthritis in vivo. METHODS: We tested the effect of A-769662, a specific AMPK agonist (60mg/kg/bid) in mouse models of antigen-induced arthritis (AIA) and passive K/BxN serum-induced arthritis. The passive K/BxN serum-induced arthritis model was also applied to AMPKα1-deficient mice. Joints were harvested and subjected to histological analysis. IL-6 expression was measured in both joint tissues and sera by ELISA. The effect of A-769662 on bone marrow derived macrophage (BMDM) response to stimulation with TLR2 and TLR4 agonists was tested in vitro. RESULTS: AMPK activation by A-769662 reduced inflammatory infiltration and joint damage in both mouse models. IL-6 expression in serum and arthritic joints was significantly decreased in A-769662-treated mice. AMPKα1 deficient mice mildly elicited an increase of clinical arthritis. IL-6 expression at both mRNA and protein levels, phosphorylation of p65 NF-κB and MAPK phosphorylation were inhibited by A-769662 in BMDMs stimulated with either TLR2 or TLR4 agonists. CONCLUSIONS: AMPK activation by specific AMPK agonist A-769662 suppressed inflammatory arthritis in mice as well as IL-6 expression in serum and arthritic joints. These data suggest that targeted activation of AMPK has a potential to be an effective therapeutic strategy for IL-6 dependent inflammatory arthritis.
Document type :
Journal articles
Complete list of metadata

Cited literature [37 references]  Display  Hide  Download
Contributor : Mireille Bos Connect in order to contact the contributor
Submitted on : Tuesday, October 20, 2015 - 10:31:12 AM
Last modification on : Wednesday, October 27, 2021 - 2:51:38 PM
Long-term archiving on: : Friday, April 28, 2017 - 7:52:13 AM


Publisher files allowed on an open archive




Monica Guma, yun Wang, Benoit Viollet, Ru Liu-Bryan. AMPK Activation by A-769662 Controls IL-6 Expression in Inflammatory Arthritis. PLoS ONE, Public Library of Science, 2015, 10 (10), pp.e0140452. ⟨10.1371/journal.pone.0140452⟩. ⟨inserm-01217825⟩



Record views


Files downloads