Up-regulation of functional kinin B1 receptors in allergic airway inflammation.
B1 receptors are known to be induced during allergic airway inflammation in animal models. However, little is known regarding in vivo B1 receptor expression in humans. We examined B1 receptor mRNA expression in nasal tissue samples from allergic rhinitis and normal subjects. Allergic rhinitis subjects displayed significantly higher expression of B1 receptor mRNA than did the normal subjects, and nasal allergen challenge increased B1 receptor mRNA expression at 8 to 24 h time points in allergic rhinitis subjects. No significant difference was found in B2 receptor expression. To confirm B2 and B1 receptor functional activity, subjects were challenged with kinin agonists. Nasal challenge with the B1 receptor ligand, Lys-des-Arg-bradykinin (BK), activated extracellular signal-regulated kinase in allergic rhinitis, but not normal, subjects. Nasal challenge with the B2 receptor ligand, BK, activated extracellular signal-regulated kinase in both allergic rhinitis and normal subjects. The consequences of B1 receptor activation were investigated using the human airway epithelial cell lines A549 and BEAS-2B. We demonstrated that Lys-des-Arg-BK activates the transcription factor AP-1. Taken together, these results show that functional B1 receptors are induced in the airway during allergic inflammation and suggest that they participate in the regulation of gene expression.
Christiansen
Sandra C
SC
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Eddleston
Jane
J
Woessner
Katharine M
KM
Chambers
Sandra S
SS
Ye
Richard
R
Pan
Zhixing K
ZK
Zuraw
Bruce L
BL
D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D016022:Case-Control Studies; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007609:Kallidin / Q000008:administration & dosage / Q000031:analogs & derivatives; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009299:Nasal Provocation Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics*; D012221:Rhinitis, Allergic, Perennial / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
D000485:Allergens; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D018808:Transcription Factor AP-1; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; D020928:Mitogen-Activated Protein Kinases; D001920:Bradykinin