2012-06-01
Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1β and inhibited by peroxisome proliferator activated receptor α agonist
Publication
Publication
Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases , Volume 71 - Issue 6 p. 1012- 1018
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 E2were 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 PGE2release 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.
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| doi.org/10.1136/annrheumdis-2011-200688, hdl.handle.net/1765/39235 | |
| Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Clockaerts, S., Bastiaansen-Jenniskens, Y., Feijt, C., de Clerck, L. S., Verhaar, J., Zuurmond, A.-M., … van Osch, G. (2012). Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1β and inhibited by peroxisome proliferator activated receptor α agonist. Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases, 71(6), 1012–1018. doi:10.1136/annrheumdis-2011-200688 |
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