Regulation of kinin receptors in airway epithelial cells by inflammatory cytokines and dexamethasone

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-1beta 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-1 receptor protein expression following both interleukin-1beta 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-1beta treatment. Arachidonic acid release in response to bradykinin was markedly enhanced by prior incubation with interleukin-1beta and this was prevented by the prior addition of dexamethasone. (C) 2002 Elsevier Science B.V. All rights reserved.