n-3 and n-6 Polyunsaturated fatty acids induce the expression of COX-2 via PPARγ activation in human keratinocyte HaCaT cells

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• 作者：Gé ; rald Chê ; ne ; Marc Dubourdeau ; Patricia Balard ; Laure Escoubet-Lozach ; Claudine Orfila ; Antoine Berry ; José ; Bernad ; Marie-Franç ; oise Aries ; Marie Charveron ; Bernard Pipy
• 关键词：Phospholipase A2 ; Inflammatory response ; Nuclear receptor
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2007
• 出版时间：May 2007
• 年：2007
• 卷：1771
• 期：5
• 页码：576-589
• 全文大小：1350 K

文摘

Polyunsaturated fatty acids (PUFA) n-3 inhibit inflammation, in vivo and in vitro in keratinocytes. We examined in HaCaT keratinocyte cell line whether eicosapentaenoic acid (EPA) a n-3 PUFA, gamma-linoleic acid (GLA) a n-6 PUFA, and arachidic acid a saturated fatty acid, modulate expression of cyclooxygenase-2 (COX-2), an enzyme pivotal to skin inflammation and reparation. We demonstrate that only treatment of HaCaT with GLA and EPA or a PPARγ ligand (roziglitazone), induced COX-2 expression (protein and mRNA). Moreover stimulation of COX-2 promoter activity was increased by those PUFAs or rosiglitazone. The inhibitory effects of GW9662 and T0070907 (PPARγ antagonists), on COX-2 expression and on stimulation of COX-2 promoter activity by EPA and GLA suggest that PPARγ is implicated in COX-2 induction. Finally, PLA2 inhibitor methyl arachidonyl fluorophosphonate blocked the PUFA effects on COX-2 induction, promoter activity and arachidonic acid mobilization suggesting involvement of AA metabolites in PPAR activation. These findings demonstrate that n-3 and n-6 PUFA increased PPARγ activity is necessary for the COX-2 induction in HaCaT human keratinocyte cells. Given the anti-inflammatory properties of EPA, we suggest that induction of COX-2 in keratinocytes may be important in the anti-inflammatory and protective mechanism of action of PUFAs n-3 or n-6.