title: Palmitate induces COX-2 expression via the sphingolipid pathway-mediated activation of NF-κB, p38, and ERK in human dermal fibroblasts.
abstract: It has been suggested that free fatty acids (FFA) such as palmitate, which are secreted from enlarged adipocytes in the subcutaneous fat of obese subjects, serve as a link between obesity and altered skin functions. Cyclooxygenease-2 (COX-2) and prostanoids participate in the induction of impaired dermal function. In the current study, we investigated the issue of whether palmitate induces COX-2 expression via the sphingolipid pathway-mediated activation of NF-κB or mitogen-activated protein kinase (MAPK) pathways in human dermal fibroblasts. Palmitate treatment significantly induced COX-2 expression and prostaglandin E2 (PGE2) release in human dermal fibroblasts. In addition, pre-treatment with triacsin C, an inhibitor of acyl-CoA synthetase in de novo ceramide synthesis, was found to reduce palmitate-induced COX-2 expression and PGE2 release in human dermal fibroblast. The findings also show that palmitate-induced COX-2 expression and PGE2 release are mediated by the NF-κB, p38, and extracellular signal-regulated kinase (ERK) MAPK pathways. These findings point to a new mechanism for explaining the link between increased FFAs in obesity and impaired dermal function.
authors: Institute of Hansen's Disease, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Korea.
authors: Eunhye
authors: E
authors: Oh
authors: Mihee
authors: M
authors: Yun
authors: Seong Keun
authors: SK
authors: Kim
authors: Gimoon
authors: G
authors: Seo
authors: Joon Sung
authors: JS
authors: Bae
authors: Kwon
authors: K
authors: Joo
authors: Gue Tae
authors: GT
authors: Chae
authors: Seong-Beom
authors: SB
authors: Lee
mesh_terms: D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009765:Obesity; D010168:Palmitates / Q000494:pharmacology*; D013107:Sphingolipids / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D002518:Ceramides; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D010168:Palmitates; D013107:Sphingolipids; D014226:Triazenes; C034613:triacsin C; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003066:Coenzyme A Ligases; D015232:Dinoprostone