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

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• 作者：Jeong June Choi^a ; Min Young Park^a ; Hwa Jin Lee^b ; Do-young Yoon^c ; Yoongho Lim^c ; Jin Won Hyun^d ; Christos C. Zouboulis^e ; Mirim Jin^a ; ^{mirimj@dju.ac.kr}
• 关键词：TNF-伪 ; Sebocyte ; Lipogenesis ; JNK ; Akt ; SZ95 human sebocytes
• 刊名：Journal of Dermatological Science
• 出版年：2012
• 期刊代码：153_09231811
• 类别：med
• 出版时间：March, 2012
• 卷：65
• 期：3
• 页码：179-188
• 文件大小：1249 K

摘要

Background

Tumor necrosis factor-alpha (TNF-伪) is an important pathophysiologic factor involved in the development of acne. However, its role is unclear.

Objective

To explore the lipogenic effect by TNF-伪 and possible molecular mechanisms in sebocyte.

Methods

Using SZ95 human sebocytes, lipid formation by TNF-伪 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-伪-induced lipogenesis was investigated by molecule specific small interfering RNA and inhibitors.

Results

TNF-伪 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-伪-induced expression of FAS and SREBP-1. TNF-伪 could not induce both expression of lipogenic proteins and lipid synthesis when Akt expression was attenuated with siRNA.

Conclusions

TNF-伪 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.