Molecular structure and transcriptional regulation by nuclear factor-kappa B of the mouse kinin B-1 receptor gene

Kinins are important mediators in cardiovascular homeostasis, inflammation, and nociception. Two kinin receptors have been described, B-1 and B-2. the B-1 receptor is normally absent in healthy tissues, but is highly induced under pathological conditions. To understand the molecular mechanism of B-1 receptor up-regulation, we determined the mouse B-1 receptor gene structure, isolated and characterized the promoter region and studied its transcriptional regulation. the mouse B-1 receptor gene contains two exons (with the entire coding region located in the second exon) and a TATA-less promoter with multiple transcription start sites. A 7.7-kbp portion of the 5'-flanking region was examined for promoter activity in vascular smooth muscle cells (VSMCs). A minimal 92-bp fragment, located immediately upstream of the transcription start region, exerted basal and lipopolysaccharide (LPS)-inducible transcription activity in the sense and antisense orientation, and was thereby identified as an enhancer element. Nuclear extracts from VSMCs showed basal and LPS-inducible binding activity of nuclear factor (NF)-kappa B at this sequence. B-1 receptor transcription activation in response to LPS was abolished by cotransfection with I kappa B alpha Delta N, an NF-kappa B repressor. in summary, our results reveal the structure of the mouse B-1 receptor gene and the involvement of NF-kappa B in the inducible mouse kinin B-1 receptor expression under pathological conditions.Universidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniv Mogi Cruzes, BR-08780911 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023062 São Paulo, BrazilCHU Rangueil, Inst Louis Bugnard, INSERM, U388, F-31052 Toulouse, FranceMax Delbruck Ctr Mol Med, D-13092 Berlin, GermanyUniversidade Federal de São Paulo, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023062 São Paulo, BrazilWeb of Scienc