Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production
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 arthrit...
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| Format: | Article |
| Language: | English |
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Wiley
2009-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2009/345838 |
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| author | Katriina Vuolteenaho Anna Koskinen Meiju Kukkonen Riina Nieminen Unto Päivärinta Teemu Moilanen Eeva Moilanen |
| author_facet | Katriina Vuolteenaho Anna Koskinen Meiju Kukkonen Riina Nieminen Unto Päivärinta Teemu Moilanen Eeva Moilanen |
| author_sort | Katriina Vuolteenaho |
| collection | DOAJ |
| description | 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 factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway c-Jun NH2-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, and PGE2, and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, and PGE2 production 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. |
| format | Article |
| id | doaj-art-73c7a9afa3764a409d7b30c2c8c597d8 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-73c7a9afa3764a409d7b30c2c8c597d82025-02-03T01:26:32ZengWileyMediators of Inflammation0962-93511466-18612009-01-01200910.1155/2009/345838345838Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 ProductionKatriina Vuolteenaho0Anna Koskinen1Meiju Kukkonen2Riina Nieminen3Unto Päivärinta4Teemu Moilanen5Eeva Moilanen6The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, 33014 University of Tampere, Tampere, FinlandThe Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, 33014 University of Tampere, Tampere, FinlandThe Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, 33014 University of Tampere, Tampere, FinlandThe Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, 33014 University of Tampere, Tampere, FinlandCoxa Hospital for Joint Replacement, P.O. Box 652, 33101 Tampere, FinlandThe Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, 33014 University of Tampere, Tampere, FinlandThe Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, 33014 University of Tampere, Tampere, FinlandObesity 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 factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway c-Jun NH2-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, and PGE2, and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, and PGE2 production 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.http://dx.doi.org/10.1155/2009/345838 |
| spellingShingle | Katriina Vuolteenaho Anna Koskinen Meiju Kukkonen Riina Nieminen Unto Päivärinta Teemu Moilanen Eeva Moilanen Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production Mediators of Inflammation |
| title | Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production |
| title_full | Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production |
| title_fullStr | Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production |
| title_full_unstemmed | Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production |
| title_short | Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production |
| title_sort | leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage mediator role of no in leptin induced pge2 il 6 and il 8 production |
| url | http://dx.doi.org/10.1155/2009/345838 |
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