NF-κB is involved in the TNF-α induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARγ expression

Abstract

TNF-α, a trimeric cytokine, was known to inhibit differention of preadipocytes to adipocytes. In the present study, we investigated signal mediators working downstream of TNF-α using murine 3T3-L1 cells. TNF-α induced activation of both c-jun NH2-terminal kinase (JNK) and nuclear transcription factor-κB (NF-κB) in 3T3-L1 cells. Blockage of these two mediators activities by specific inhibitors, SP600125 and Ad-IκBα-SR restored adipogenesis differentiation suggesting their involvement in the inhibited differentiation of 3T3-L1 cells by TNF-α. Consistent with previous studies, peroxisome proliferator-activated receptor gamma (PPARγ) a key transcriptional regulator was remarkably reduced by TNF-α treatment. Compared with adipogenesis, however, SP600125, a chemical JNK inhibitor hardly relieved TNF-α effect on PPARγ expression whereas S32A/S36A mutant of IκBα considerably recovered PPARγ 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-α is partly implemented through NF-κB and one of its downstream effectors be PPARγ.