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Apremilast,a novel PDE4 inhibitor,inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis
Authors:Fiona E McCann  Andrew C Palfreeman  Melanie Andrews  Dany P Perocheau  Julia J Inglis  Peter Schafer  Marc Feldmann  Richard O Williams  Fionula M Brennan
Institution:(1) The Kennedy Institute of Rheumatology, Imperial College London, 65 Aspenlea Road, London, W6 8LH, UK;(2) Institute for Molecular Bioscience, University of Queensland, Bldg 80 Services Road, Brisbane, QLD, 4072, Australia;(3) Pharmacology & Anaesthesiology Unit, School of Medicine & Pharmacology, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia;(4) Translational Development, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07901, USA
Abstract:

Introduction  

Type 4 phosphodiesterases (PDE4) play an important role in immune cells through the hydrolysis of the second messenger, cAMP. Inhibition of PDE4 has previously been shown to suppress immune and inflammatory responses, demonstrating PDE4 to be a valid therapeutic target for immune-mediated pathologies. We assessed the anti-inflammatory effects of a novel PDE4 inhibitor, apremilast, in human synovial cells from rheumatoid arthritis (RA) patients, as well as two murine models of arthritis.
Keywords:
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