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

• Published in: European journal of pharmacology 2002-04, Vol.441 (3), p.193-202
• Main Authors: Newton, Robert, Eddleston, Jane, Haddad, El-Bdaoui, Hawisa, Samia, Mak, Judith, Lim, Sam, Fox, Alison J., Donnelly, Louise E., Fan Chung, K.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Bradykinin; Bradykinin B 1 receptor; Bradykinin B 2 receptor; Bronchi - cytology; Bronchi - drug effects; Bronchi - metabolism; Cells, Cultured; Cyclooxygenase; Cytokines - pharmacology; Cytokines - physiology; Des-Arg 10-kallidin; Dexamethasone; Dexamethasone - pharmacology; Dinoprostone - biosynthesis; Dinoprostone - metabolism; Dose-Response Relationship, Drug; Epithelial cell; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Humans; Inflammation - metabolism; Medical sciences; Pharmacology. Drug treatments; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Receptors, Bradykinin - biosynthesis; Respiratory system; RNA, Messenger - biosynthesis
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01624-7

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.