Palmitate induces COX-2 expression via the sphingolipid pathway-mediated activation of NF-κB, p38, and ERK in human dermal fibroblasts

• Published in: Archives of Dermatological Research Vol. 306; no. 4; pp. 339 - 345
• Main Authors: Oh, Eunhye, Yun, Mihee, Kim, Seong Keun, Seo, Gimoon, Bae, Joon Sung, Joo, Kwon, Chae, Gue Tae, Lee, Seong-Beom
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2014
• Subjects: Cells, Cultured; Ceramides - biosynthesis; Coenzyme A Ligases - antagonists & inhibitors; Cyclooxygenase 2 - biosynthesis; Dermatology; Dinoprostone - secretion; Enzyme Inhibitors - pharmacology; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - biosynthesis; Fibroblasts - metabolism; Humans; Medicine; Medicine & Public Health; NF-kappa B - antagonists & inhibitors; NF-kappa B - biosynthesis; Obesity; Original Paper; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - biosynthesis; Palmitates - pharmacology; Sphingolipids - metabolism; Triazenes - pharmacology; Sphingolipid pathway; Dermal fibroblast; Cyclooxygenase-2; Palmitate
• ISSN: 0340-3696; 1432-069X; 1432-069X
• DOI: 10.1007/s00403-013-1434-6

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 E 2 (PGE 2 ) 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 PGE 2 release in human dermal fibroblast. The findings also show that palmitate-induced COX-2 expression and PGE 2 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.