Novel kinin B₁ receptor splice variant and 5'UTR regulatory elements are responsible for cell specific B₁ receptor expression.
The kinin B₁ receptor (B₁R) is rapidly upregulated after tissue trauma or inflammation and is involved in cancer and inflammatory diseases such as asthma. However, the role of the: promoter; a postulated alternative promoter; and spliced variants in airway epithelial and other lung cells are poorly understood. We identified, in various lung cell lines and leucocytes, a novel, naturally occurring splice variant (SV) of human B₁R gene with a shorter 5'untranslated region. This novel SV is ≈35% less stable than the wild-type (WT) transcript in lung adenocarcinoma cells (H2126), but does not influence translation efficiency. Cell-specific differences in splice variant expression were observed post des[Arg10]-kallidin stimulation with delayed upregulation of SV compared to WT suggesting potentially different regulatory responses to inflammation. Although an alternative promoter was not identified in our cell-lines, several cell-specific regulatory elements within the postulated alternative promoter region (negative response element (NRE) -1020 to -766 bp in H2126; positive response element (PRE) -766 to -410 bp in 16HBE; -410 to +1 region acts as a PRE in H2126 and NRE in 16HBE cells) were found. These findings reveal complex regulation of B₁R receptor expression in pulmonary cells which may allow future therapeutic manipulation in chronic pulmonary inflammation and cancer.
Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia (LIWA), Perth, Western Australia, Australia ; Centre for Asthma, Allergy and Respiratory Research (CAARR), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Faang Y
FY
Cheah
Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia (LIWA), Perth, Western Australia, Australia ; Centre for Asthma, Allergy and Respiratory Research (CAARR), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Svetlana
S
Baltic
Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia (LIWA), Perth, Western Australia, Australia ; Centre for Asthma, Allergy and Respiratory Research (CAARR), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Suzanna E L
SE
Temple
Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia (LIWA), Perth, Western Australia, Australia ; Centre for Asthma, Allergy and Respiratory Research (CAARR), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia ; Department of Cellular Pathology, Ausiral University of Chile, Valdivia, Chile.
Kanti
K
Bhoola
Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia (LIWA), Perth, Western Australia, Australia ; Centre for Asthma, Allergy and Respiratory Research (CAARR), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia ; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Western Australia, Perth, Western Australia, Australia.
Philip J
PJ
Thompson
D020121:5' Untranslated Regions / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics*; D000704:Analysis of Variance; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043783:Receptor, Bradykinin B1 / Q000235:genetics* / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D020121:5' Untranslated Regions; D017931:DNA Primers; D043783:Receptor, Bradykinin B1