Ag. Ni et al., TRANSCRIPTION FACTOR NUCLEAR FACTOR KAPPA-B REGULATES THE INDUCIBLE EXPRESSION OF THE HUMAN B-1 RECEPTOR GENE IN INFLAMMATION, The Journal of biological chemistry, 273(5), 1998, pp. 2784-2791
Expression of the bradykinin B-1 receptor gene is upregulated in vascu
lar smooth muscle cells (VSMCs) in response to a variety of inflammato
ry stimuli. We isolated the 5'-flanking region of the human bradykinin
B-1 receptor gene and examined its promoter activity by transient tra
nsfection analysis. This region (-2582 to +34) showed promoter activit
y inducible by lipopolysaccharide (LPS), tumor necrosis factor alpha (
TNF-alpha), and interleukin-1 beta (IL-1 beta) in VSMCs. Further delet
ion analysis revealed that constructs containing 111 base pairs of 5'-
flanking sequence were sufficient for transcriptional induction. Mutag
enesis of a nuclear factor ICE (NF-KB)like site at -64 to -55 abolishe
d most of the LPS, TNF-alpha; and IL-1 beta inducibility, whereas a mu
tation of a cyclic AMP response element at -50 to -43 markedly reduced
the basal promoter activity, and a mutation of the activator protein
1 (AP-1) site at -78 to -72 had minimal effects. Nuclear extracts from
LPS, TNF-alpha, and IL-1 beta-treated VSMCs, IL-1 beta-treated human
hepatoma HepG(2), and human lung fibroblast IMR-90 cells showed strong
. inducible binding activity to the NF-kappa B-like site by gel shift
assays. These results demonstrated that NF-kappa B-like nuclear factor
was involved in the inducible expression of the human bradykinin B-1
receptor gene during inflammatory processes.