NF-kappaB is involved in the TNF-alpha induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARgamma expression.
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 NH(2)-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.
Chae
Gi-Nam
GN
Department of Biochemistry, College of Medicine, Dankook University, San 29 Anseo-dong, Cheonan 330-714, Korea.
Kwak
Sahng-June
SJ
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha