The regulation of the human tumor necrosis factor alpha promoter region in macrophage, T cell, and B cell lines.

摘要: The 1311-base pair human tumor necrosis factor (TNF) alpha promoter region was fused to the luciferase (Luc) reporter gene and studied in a transient transfection system three TNF producing cell lines, U937 macrophage line, MLA 144 T 729-6 B line. This full length construct can be induced by phorbol 13-myristate acetate (PMA) each of these types. Analysis series 5'-truncations showed several peaks basal PMA activity suggesting presence positive negative regulatory elements. A responsive element localized between -95 -36 bp relative transcription start site. Within this region, single AP-2- AP-1-like consensus sequences were noted. These AP-2 AP-1 sites modified with double point mutation. modest (20-50%) reduction observed site However, mutation markedly diminished both PMA-activated activity. Also co-transfections wild-type an AP-1/c-jun expression vector resulted augmented PMA-induced