Mechanism of cigarette smoke-induced kinin B(1) receptor expression in rat airways.
Pulmonary inflammation is an important pathological feature of tobacco smoke related lung diseases such as chronic obstructive pulmonary disease (COPD). Kinin type 1 and type 2 receptors (B(1)R, B(2)R) are known to be associated with inflammatory responses of the lungs and other organs. In this study, we investigated whether cigarette smoke-induced airway inflammation could up-regulate B(1)R and B(2)R in correlation with IL-1β and TNF-α. Rat lung slices treated with 5 μg/ml total particulate matter (TPM) of cigarette smoke for 24 h showed an enhanced expression of B(1)R and IL-1β by 5-fold and 30-fold, respectively, in comparison to vehicle treatment (dimethyl sulfoxide). However, higher concentrations of TPM failed to induce B(1)R. No significant increase of B(2)R or TNF-α gene induction was observed. IL-1 receptor antagonist (IL-1Ra, 2 ng/ml) significantly blocked B(1)R gene induction by TPM, while 500 μM pentoxifylline, TNF-α inhibitor, reduced it partially. Western blot analysis showed a 2-fold enhanced expression of B(1)R in rat lung slices treated with 5 μg/ml TPM for 24 h and such protein expression was totally blocked by a co-treatment with IL-1Ra but not with pentoxifylline. In addition to the lower airways, rat trachea subchronically exposed to cigarette whole smoke exhibited 11-fold B(1)R gene induction in comparison with those exposed only to air. Our results demonstrate the involvement of B(1)R in cigarette smoke-induced airway inflammation through a mechanism which is mediated by the pro-inflammatory cytokine IL-1β.
Lin
James Chi-Jen
JC
Imperial Tobacco Canada Ltd, 3711 Saint Antoine West, Montréal, QC, Canada H4C 3P6.
Talbot
Sébastien
S
Lahjouji
Karim
K
Roy
Jean-Philippe
JP
Sénécal
Jacques
J
Couture
Réjean
R
Morin
André
A
D000818:Animals; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
D053583:Interleukin-1beta; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D012906:Smoke