Title
Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1β and inhibited by peroxisome proliferator activated receptor α agonist
Author
Clockaerts, S.
Bastiaansen-Jenniskens, Y.M.
Feijt, C.
Clerck, L.de
Verhaar, J.A.N.
Zuurmond, A.M.
Stojanovic-Susulic, V.
Somville, J.
Kloppenburg, M.
van Osch, G.J.V.M.
Publication year
2012
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)1β and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor α (PPARα), which is also activated by lipid-lowering drugs such as fi brates. Methods: Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (fi ve donors) and synovium (six donors) were cultured with IL-1β and PPARα agonist Wy14643. Gene expression of IL-1β, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)α, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNFα, MCP1 and prostaglandin E 2 were compared with unstimulated IPFP and synovium explants. Results: IPFP released large amounts of infl ammatory cytokines, adipokines and growth factors. IL-1β increased gene expression of PTGS2, TNFα, IL-1β, IL-6 and VEGF and increased TNFα release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE 2 release did not increase signifi cantly. Synovium responded to IL-1βsimilarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1β, TNFα, MCP1, VEGF and leptin in IPFP explants and IL-1β, TNFα, IL-6, IL-10 and VEGF in synovium that responded to IL-1β. Conclusion: IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1β and decreased by a PPARα agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating infl ammatory properties of IPFP and synovium.
Subject
Healthy for Life
Healthy Living
Life
MHR - Metabolic Health Research
EELS - Earth, Environmental and Life Sciences
To reference this document use:
http://resolver.tudelft.nl/uuid:4a48446d-78a4-4dcf-a77e-02043d383036
DOI
https://doi.org/10.1136/annrheumdis-2011-200688
TNO identifier
460433
ISSN
0003-4967
Source
Annals of the Rheumatic Diseases, 71 (71), 1012-1018
Document type
article