Up-regulation of bradykinin receptors in a murine in-vitro model of chronic airway inflammation.
Tumour necrosis factor-alpha (TNF-alpha) is a mediator with a likely role in chronic airway inflammation and airway hyperresponsiveness. In the present study, mouse tracheal segments were cultured for 1, 4 or 8 days in the absence and presence of TNF-alpha. Contractile response of cultured segments to des-Arg9-bradykinin and bradykinin was assessed in myographs and mRNA for bradykinin B1 and B2 receptors was quantified by real-time polymerase chain reaction. Both contraction to des-Arg9-bradykinin and bradykinin, mediated via bradykinin B1 and B2 receptors, respectively, and mRNA levels for these receptors were up-regulated following culture. These responses were markedly increased in segments treated with TNF-alpha. Experiments with SP600125 (anthrax(1,9-cd)pyrazol-6(2H)-one) and PD98059 (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) demonstrated that both intracellular c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 pathways were implicated in this process. Thus, TNF-alpha causes an increase of bradykinin contractility in mouse trachea, which at least partly is due to a transcriptional increase of bradykinin receptors.
Zhang
Yaping
Y
Department of Otorhinolaryngology, Laboratory of Clinical and Experimental Allergy Research, Malmö University Hospital, SE-205 02 Malmö, Sweden.
Adner
Mikael
M
Cardell
Lars-Olaf
LO
D000465:Algorithms; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D043783:Receptor, Bradykinin B1 / Q000096:biosynthesis; D043782:Receptor, Bradykinin B2 / Q000096:biosynthesis; D018002:Receptors, Bradykinin / Q000096:biosynthesis*; D012140:Respiratory Tract Diseases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001993:Bronchodilator Agents; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D014409:Tumor Necrosis Factor-alpha; C024626:bradykinin, des-Arg(9)-; D019001:Nitric Oxide Synthase; D020928:Mitogen-Activated Protein Kinases; D001920:Bradykinin