TNF-α increases lipogenesis via JNK and PI3K/Akt pathways in SZ95 human sebocytes.
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.
Laboratory of Pathology, College of Oriental Medicine, Daejeon University, Daejeon 300-716, Republic of Korea.
Jeong June
JJ
Choi
Min Young
MY
Park
Hwa Jin
HJ
Lee
Do-Young
DY
Yoon
Yoongho
Y
Lim
Jin Won
JW
Hyun
Christos C
CC
Zouboulis
Mirim
M
Jin
D002460:Cell Line; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000502:physiology*; D012627:Sebaceous Glands / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019014:fas Receptor / Q000187:drug effects / Q000502:physiology
D047492:Peroxisome Proliferator-Activated Receptors; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt