Regulation of kinin receptors in airway epithelial cells by inflammatory cytokines and dexamethasone |
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Authors: | Newton Robert Eddleston Jane Haddad El-Bdaoui Hawisa Samia Mak Judith Lim Sam Fox Alison J Donnelly Louise E Chung K Fan |
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Affiliation: | Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London SW3, UK. robert.newton@ic.ac.uk |
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Abstract: | The two kinin receptors, B(1) and B(2), are upregulated in inflammation and may play a role in diseases such as asthma. In pulmonary A549 cells, TNF-alpha or interleukin-1 beta dramatically increased bradykinin B(1) and B(2) receptor mRNA expression and this response was prevented by dexamethasone. In primary human bronchial epithelial cells, bradykinin B(1) receptor mRNA expression showed a similar trend, whereas bradykinin B(2) receptor showed almost constitutive expression. Radioligand-binding studies revealed significant increases in bradykinin B(2) receptor protein expression following both interleukin-1 beta and TNF-alpha treatment of A549 cells; however, no evidence was found for bradykinin B(1) receptor. Functionally, the bradykinin B(2) receptor ligand, bradykinin, but not the B(1) ligand, des-Arg(10)-kallidin, produced a marked increase in prostaglandin E(2) release when administered following interleukin-1 beta treatment. Arachidonic acid release in response to bradykinin was markedly enhanced by prior incubation with interleukin-1 beta and this was prevented by the prior addition of dexamethasone. |
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Keywords: | Bradykinin Des-Arg10-kallidin Bradykinin B1 receptor Bradykinin B2 receptor Cyclooxygenase Epithelial cell Dexamethasone |
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