PMID- 14646597 OWN - NLM STAT- MEDLINE DCOM- 20040826 LR - 20081121 IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 35 IP - 5 DP - 2003 Oct 31 TI - NF-kappaB is involved in the TNF-alpha induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARgamma expression. PG - 431-7 AB - 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. FAU - Chae, Gi-Nam AU - Chae GN AD - Department of Biochemistry, College of Medicine, Dankook University, San 29 Anseo-dong, Cheonan 330-714, Korea. FAU - Kwak, Sahng-June AU - Kwak SJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/cytology/drug effects MH - Animals MH - Cell Differentiation/*drug effects MH - Gene Expression Regulation/*drug effects MH - Mice MH - NF-kappa B/*metabolism MH - Promoter Regions, Genetic/genetics MH - RNA, Messenger/genetics/metabolism MH - Receptors, Cytoplasmic and Nuclear/*genetics MH - Transcription Factors/*genetics MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2003/12/04 05:00 MHDA- 2004/08/27 05:00 CRDT- 2003/12/04 05:00 PHST- 2003/12/04 05:00 [pubmed] PHST- 2004/08/27 05:00 [medline] PHST- 2003/12/04 05:00 [entrez] AID - 2003103113 [pii] AID - 10.1038/emm.2003.56 [doi] PST - ppublish SO - Exp Mol Med. 2003 Oct 31;35(5):431-7. doi: 10.1038/emm.2003.56.