Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1 beta and inhibited by peroxisome proliferator activated receptor alpha agonist

Stefan Clockaerts, Yvonne Jenniskens, C Feijt, L De Clerck, Jan Verhaar, AM Zuurmond, V Stojanovic-Susulic, J Somville, M Kloppenburg, Gerjo van Osch

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background Infrapatellar fat pad (IPFP) might be involved in osteoarthritis (OA) by production of cytokines. It was hypothesised that production of cytokines is sensitive to environmental conditions. Objectives To evaluate cytokine production by IPFP in response to interleukin (IL)1b and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor alpha (PPAR alpha), which is also activated by lipid-lowering drugs such as fibrates. Methods Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (five donors) and synovium (six donors) were cultured with IL-1b and PPAR alpha agonist Wy14643. Gene expression of IL-1b, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)alpha, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNF alpha, MCP1 and prostaglandin E-2 were compared with un Results IPFP released large amounts of inflammatory cytokines, adipokines and growth factors. IL-1b increased gene expression of PTGS2, TNF alpha, IL-1b, IL-6 and VEGF and increased TNF alpha release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE(2) release did not increase significantly. Synovium responded to IL-1b similarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1b, TNF alpha, MCP1, VEGF and leptin in IPFP explants and IL Conclusion IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1b and decreased by a PPAR alpha agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating inflammatory properties of IPFP and synovium.
Original languageUndefined/Unknown
Pages (from-to)1012-1018
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume71
Issue number6
DOIs
Publication statusPublished - 2012

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