PMID- 22305016 OWN - NLM STAT- MEDLINE DCOM- 20120709 LR - 20171116 IS - 1873-569X (Electronic) IS - 0923-1811 (Linking) VI - 65 IP - 3 DP - 2012 Mar TI - TNF-alpha increases lipogenesis via JNK and PI3K/Akt pathways in SZ95 human sebocytes. PG - 179-88 LID - 10.1016/j.jdermsci.2011.11.005 [doi] AB - 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. CI - Copyright (c) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. FAU - Choi, Jeong June AU - Choi JJ AD - Laboratory of Pathology, College of Oriental Medicine, Daejeon University, Daejeon 300-716, Republic of Korea. FAU - Park, Min Young AU - Park MY FAU - Lee, Hwa Jin AU - Lee HJ FAU - Yoon, Do-Young AU - Yoon DY FAU - Lim, Yoongho AU - Lim Y FAU - Hyun, Jin Won AU - Hyun JW FAU - Zouboulis, Christos C AU - Zouboulis CC FAU - Jin, Mirim AU - Jin M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111120 PL - Netherlands TA - J Dermatol Sci JT - Journal of dermatological science JID - 9011485 RN - 0 (Peroxisome Proliferator-Activated Receptors) RN - 0 (SREBF1 protein, human) RN - 0 (Sterol Regulatory Element Binding Protein 1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (fas Receptor) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Cell Line MH - Humans MH - Lipid Metabolism/drug effects MH - Lipogenesis/*drug effects MH - MAP Kinase Signaling System/drug effects/*physiology MH - Peroxisome Proliferator-Activated Receptors/drug effects/physiology MH - Phosphatidylinositol 3-Kinases/drug effects/*physiology MH - Proto-Oncogene Proteins c-akt/drug effects/*physiology MH - Sebaceous Glands/*cytology/drug effects/metabolism MH - Signal Transduction/*drug effects/physiology MH - Sterol Regulatory Element Binding Protein 1/physiology MH - Tumor Necrosis Factor-alpha/*pharmacology MH - fas Receptor/drug effects/physiology EDAT- 2012/02/07 06:00 MHDA- 2012/07/10 06:00 CRDT- 2012/02/07 06:00 PHST- 2011/06/29 00:00 [received] PHST- 2011/11/11 00:00 [revised] PHST- 2011/11/12 00:00 [accepted] PHST- 2012/02/07 06:00 [entrez] PHST- 2012/02/07 06:00 [pubmed] PHST- 2012/07/10 06:00 [medline] AID - S0923-1811(11)00321-5 [pii] AID - 10.1016/j.jdermsci.2011.11.005 [doi] PST - ppublish SO - J Dermatol Sci. 2012 Mar;65(3):179-88. doi: 10.1016/j.jdermsci.2011.11.005. Epub 2011 Nov 20.