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

JIANG Yong^*, LIU Ai-Hua, HUANG Qiao-Bing and ZHAO Ke-Seng
( Key Laboratory for Shock and Microcirculation of PLA , Department of Pathophysiology,
The First Military Medical University, Guangzhou 510515, China )

Abstract　　The luciferase reporter gene system driven by the TNF-α promoter was constructed for the studies of the effect of p38 MAPK signal transduction pathway on the gene expression of TNF-α. 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-α reporter gene transcription. The induction of TNF-α 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-α 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-α promoter activity induced by MKK6b(E) or LPS. All these results suggest that a possible mechanism for TNF-α 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-α gene expression induced by LPS.
Key Words　　Lipopolysaccharide; tumor necrosis factor; gene expression; p38 MAPK

Corresponding author: Tel, 86-20-87705370-48240; Fax, 86-20-87705671; e-mail, [email protected]