Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-InducedPGE2, IL-6, and IL-8 Production

Mediators of Inflammation - Tập 2009 - Trang 1-10 - 2009
Katriina Vuolteenaho1, Anna Koskinen1, Meiju Kukkonen1, Riina Nieminen1, Unto Päivärinta2, Teemu Moilanen2,1, Eeva Moilanen1
1The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, 33014 University of Tampere, Tampere, Finland
2Coxa Hospital for Joint Replacement, P.O. Box 652, 33101, Tampere, Finland

Tóm tắt

Obesity is an important risk factor for osteoarthritis (OA) in weight-bearing joints, but also in hand joints, pointing to an obesity-related metabolic factor that influences on the pathogenesis of OA. Leptin is an adipokine regulating energy balance, and it has recently been related also to arthritis and inflammation as a proinflammatory factor. In the present paper, the effects of leptin on human OA cartilage were studied. Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO,PGE2, IL-6, and IL-8. The results suggest that the effects of leptin are mediated through activation of transcription factor nuclear factorκB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway c-JunNH2-terminal kinase (JNK). Interestingly, inhibition of leptin-induced NO production with a selective iNOS inhibitor 1400 W inhibited also the production of IL-6, IL-8, andPGE2, and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, andPGE2production are dependent on NO. These findings support the idea of leptin as a factor enhancing the production of proinflammatory factors in OA cartilage and as an agent contributing to the obesity-associated increased risk for osteoarthritis.

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Mediators of Inflammation

Tập 2009

1-10

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