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

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-α or interleukin-1β 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-1β and TNF-α 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-1β treatment. Arachidonic acid release in response to bradykinin was markedly enhanced by prior incubation with interleukin-1β and this was prevented by the prior addition of dexamethasone.