TNF-α increases lipogenesis via JNK and PI3K/Akt pathways in SZ95 human sebocytes

Background: Tumor necrosis factor-alpha (TNF-alpha) is an important pathophysiologic factor involved in the development of acne. However, its role is unclear. Objective: To explore the lipogenic effect by TNF-alpha and possible molecular mechanisms in sebocyte. Methods: Using SZ95 human sebocytes, lipid formation by TNF-alpha was assessed by Oil Red O, Nile Red staining and thin layer chromatography (TLC). Expression of lipogenic genes and activation of mitogen-activated protein kinase as well as Akt were examined by real-time polymerase chain reaction and/or Western blot analysis. Activation of peroxisome proliferator-activated receptor (PPAR) was evaluated by luciferase assay using PPAR response element containing reporter plasmids. Involvement of c-Jun N-terminal kinase (JNK) and Akt in TNF-alpha-induced lipogenesis was investigated by molecule specific small interfering RNA and inhibitors. Results: TNF-alpha treatment significantly increased formation of lipid droplets in accordance with up-regulated expression of FAS and activation of SREBP-1, but not PPARs. Suppression of phosphorylated JNK by the JNK inhibitor SP600125 greatly diminished TNF-alpha-induced expression of FAS and SREBP-1. TNF-alpha could not induce both expression of lipogenic proteins and lipid synthesis when Akt expression was attenuated with siRNA. Conclusions: TNF-alpha induces lipogenesis in SZ95 human sebocytes through the JNK and phosphoinositide-3-kinase/Akt pathways. These results will be valuable in developing therapeutic strategies for control of seborrhea and acne. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.