Targeting the P2X7 receptor in rheumatoid arthritis: biological rationale for P2X7 antagonism

McInnes, I. B. , Cruwys, S., Bowers, K. and Braddock, M. (2014) Targeting the P2X7 receptor in rheumatoid arthritis: biological rationale for P2X7 antagonism. Clinical and Experimental Rheumatology, 32(6), pp. 878-882. (PMID:25288220)

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Publisher's URL: https://www.clinexprheumatol.org/abstract.asp?a=7714

Abstract

Objectives: This paper aims to explore the functional significance of the P2X7 receptor in preclinical models of rheumatoid arthritis. Methods: Preclinical studies in vivo were performed using the rat streptococcal cell wall (SCW) arthritis model. Ex vivo cultures of lipopolysaccharide (LPS)/benzoylbenzoyl adenosine triphosphate (BzATP)-stimulated human monocytes were generated to test the activities of a novel, highly specific inhibitor of human P2X7, AZD9056, on interleukin (IL)-1 and IL-18 release. Results: P2X7 receptor expression was detected in inflamed synovial tissue after onset of SCW-induced arthritis in rats. Inhibition of P2X7 therein led to reduced articular inflammation and erosive progression. No effect was noted on acute-phase responses. Ex vivo, AZD9056 inhibited IL-1 and IL-18 release to BzATP in LPS-primed human monocytes. Conclusions: P2X7 receptor inhibition could represent a novel approach to the treatment of inflammatory arthritis. However, confirmatory clinical studies are warranted to further explore this possibility.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain
Authors: McInnes, I. B., Cruwys, S., Bowers, K., and Braddock, M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Clinical and Experimental Rheumatology
Publisher:Pacini Editore SpA
ISSN:0392-856X
ISSN (Online):0392-856X

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