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-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.
Newton
Robert
R
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London SW3, UK. robert.newton@ic.ac.uk
Eddleston
Jane
J
Haddad
El-Bdaoui
el-B
Hawisa
Samia
S
Mak
Judith
J
Lim
Sam
S
Fox
Alison J
AJ
Donnelly
Louise E
LE
Chung
K Fan
KF
D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000096:biosynthesis*
D016207:Cytokines; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D003907:Dexamethasone; D015232:Dinoprostone