Transcription factor nuclear factor κB regulates the inducible expression of the human B1 receptor gene in inflammation

Aiguo Ni, Lee Chao, Julie Chao

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2784-2791
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number5
DOIs
StatePublished - 30 Jan 1998

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