Abstract
Background
Tumor necrosis factor-alpha (TNF-α) is an important pathophysiologic factor involved
in the development of acne. However, its role is unclear.
Objective
To explore the lipogenic effect by TNF-α and possible molecular mechanisms in sebocyte.
Methods
Using SZ95 human sebocytes, lipid formation by TNF-α 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-α-induced
lipogenesis was investigated by molecule specific small interfering RNA and inhibitors.
Results
TNF-α 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-α-induced
expression of FAS and SREBP-1. TNF-α could not induce both expression of lipogenic
proteins and lipid synthesis when Akt expression was attenuated with siRNA.
Conclusions
TNF-α 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.
Keywords
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Article info
Publication history
Published online: February 03, 2012
Accepted:
November 12,
2011
Received in revised form:
November 11,
2011
Received:
June 29,
2011
Identification
Copyright
© 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
