NF-kappaB is involved in the TNF-alpha induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARg expression
Experimental & Molecular Medicine
;
: 431-437, 2003.
Article
in English
| WPRIM
| ID: wpr-171357
ABSTRACT
TNF-alpha, a trimeric cytokine, was known to inhibit differention of preadipocytes to adipocytes. In the present study, we investigated signal mediators working downstream of TNF-alpha using murine 3T3-L1 cells. TNF-alpha induced activation of both c-jun NH2-terminal kinase (JNK) and nuclear transcription factor-kappaB (NF-kappaB) in 3T3-L1 cells. Blockage of these two mediators activities by specific inhibitors, SP600125 and Ad-IkappaBalpha-SR restored adipogenesis differentiation suggesting their involvement in the inhibited differentiation of 3T3-L1 cells by TNF-alpha. Consistent with previous studies, peroxisome proliferator-activated receptor gamma (PPARgamma) a key transcriptional regulator was remarkably reduced by TNF-alpha treatment. Compared with adipogenesis, however, SP600125, a chemical JNK inhibitor hardly relieved TNF-alpha effect on PPARgamma expression whereas S32A/S36A mutant of IkappaBalpha considerably recovered PPARgamma expression, indicating that two signal mediators exploit separable main routes to achieve reduced adipogenesis. These results suggest that inhibition of 3T3-L1 cells differentiation by TNF-alpha is partly implemented through NF-kappaB and one of its downstream effectors be PPARgamma.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Transcription Factors
/
RNA, Messenger
/
Cell Differentiation
/
Gene Expression Regulation
/
NF-kappa B
/
Promoter Regions, Genetic
/
Tumor Necrosis Factor-alpha
/
Receptors, Cytoplasmic and Nuclear
/
Adipocytes
/
3T3-L1 Cells
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2003
Type:
Article
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