p38 MAPK Signal is Necessary for TNF-alpha Gene Expression in RAW Cells

The luciferase reporter gene system driven by the TNF-alpha promoter was constructed for the studies of the effect of p38 MAPK signal transduction pathway on the gene expression of TNF-alpha. In the experiments of co-transfection in RAW cells it was found that there was a significant relevance between the activation of p38 by LPS and the induction of TNF-alpha reporter gene transcription. The induction of TNF-alpha expression was not shown after transfection of p38 only co-transfection of p38 with the active mutant of its upstream kinase, MKK6b, however, did induce the high expression of luciferase. Further studies showed that the induction of TNF-alpha promoter activity by MKK6b(E) and LPS was similar. In addition, the dominant negative form of p38 or p38 inhibitor gave an inhibitory effect on the TNF-alpha promoter activity induced by MKK6b(E) or LPS. All these results suggest that a possible mechanism for TNF-alpha production in endotoxic shock is the increase in gene transactivity induced by LPS in monocytes/macrophages, and that p38 MAPK signal pathway participates in the regulation of TNF-alpha gene expression induced by LPS.