NF-kappaB is involved in the TNF-alpha induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARg expression.
- Author:
Gi Nam CHAE
1
;
Sahng June KWAK
Author Information
1. Department of Biochemistry, College of Medicine, Dankook University, San 29 Anseo-dong, Cheonan 330-714, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH:
3T3-L1 Cells;
Adipocytes/cytology/drug effects;
Animals;
Cell Differentiation/*drug effects;
Gene Expression Regulation/*drug effects;
Mice;
NF-kappa B/*metabolism;
Promoter Regions (Genetics)/genetics;
RNA, Messenger/genetics/metabolism;
Receptors, Cytoplasmic and Nuclear/*genetics;
Support, Non-U.S. Gov't;
Transcription Factors/*genetics;
Tumor Necrosis Factor/*pharmacology
- From:Experimental & Molecular Medicine
2003;35(5):431-437
- CountryRepublic of Korea
- Language:English
-
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.
