TY - JOUR
T1 - Transcription factor nuclear factor κB regulates the inducible expression of the human B1 receptor gene in inflammation
AU - Ni, Aiguo
AU - Chao, Lee
AU - Chao, Julie
PY - 1998/1/30
Y1 - 1998/1/30
N2 - Expression of the bradykinin B1 receptor gene is up-regulated in vascular smooth muscle cells (VSMCs) in response to a variety of inflammatory stimuli. We isolated the 5'-flanking region of the human bradykinin B1 receptor gene and examined its promoter activity by transient transfection analysis. This region (-2582 to +34) showed promoter activity inducible by lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α), and interleukin- 1β (IL-1β) in VSMCs. Further deletion analysis revealed that constructs containing 111 base pairs of 5'-flanking sequence were sufficient for transcriptional induction. Mutagenesis of a nuclear factor κB (NF-κB)like site at -64 to -55 abolished most of the LPS, TNF-α, and IL-1β inducibility, whereas a mutation 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-α, and IL-1β-treated VSMCs, IL-1β-treated human hepatoma HepG2, and human lung fibroblast IMR-90 cells showed strong inducible binding activity to the NF-κB-like site by gel shift assays. These results demonstrated that NF-κB-like nuclear factor was involved in the inducible expression of the human bradykinin B1 receptor gene during inflammatory processes.
AB - Expression of the bradykinin B1 receptor gene is up-regulated in vascular smooth muscle cells (VSMCs) in response to a variety of inflammatory stimuli. We isolated the 5'-flanking region of the human bradykinin B1 receptor gene and examined its promoter activity by transient transfection analysis. This region (-2582 to +34) showed promoter activity inducible by lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α), and interleukin- 1β (IL-1β) in VSMCs. Further deletion analysis revealed that constructs containing 111 base pairs of 5'-flanking sequence were sufficient for transcriptional induction. Mutagenesis of a nuclear factor κB (NF-κB)like site at -64 to -55 abolished most of the LPS, TNF-α, and IL-1β inducibility, whereas a mutation 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-α, and IL-1β-treated VSMCs, IL-1β-treated human hepatoma HepG2, and human lung fibroblast IMR-90 cells showed strong inducible binding activity to the NF-κB-like site by gel shift assays. These results demonstrated that NF-κB-like nuclear factor was involved in the inducible expression of the human bradykinin B1 receptor gene during inflammatory processes.
UR - http://www.scopus.com/inward/record.url?scp=0032579513&partnerID=8YFLogxK
U2 - 10.1074/jbc.273.5.2784
DO - 10.1074/jbc.273.5.2784
M3 - Article
C2 - 9446586
AN - SCOPUS:0032579513
SN - 0021-9258
VL - 273
SP - 2784
EP - 2791
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -