Mechanism of cigarette smoke-induced kinin B1 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 (B1R, B2R) 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 B1R and B2R 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 B1R 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 B1R. No significant increase of B2R or TNF-α gene induction was observed. IL-1 receptor antagonist (IL-1Ra, 2 ng/ml) significantly blocked B1R gene induction by TPM, while 500 μM pentoxifylline, TNF-α inhibitor, reduced it partially. Western blot analysis showed a 2-fold enhanced expression of B1R 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 B1R gene induction in comparison with those exposed only to air. Our results demonstrate the involvement of B1R in cigarette smoke-induced airway inflammation through a mechanism which is mediated by the pro-inflammatory cytokine IL-1β.

Research highlights▶ Expression of kinin type 1 receptor (B1R) and IL-1β is enhanced in rat lung slices treated with total particulate matter (TPM) of cigarette smoke. ▶ Induction of kinin type 2 receptor (B2R) and TNF-α gene by TPM is not significant. ▶ Protein expression of B1R is totally blocked by a co-treatment with IL-1Ra, a IL-1 receptor antagonist. ▶ B1R is involved in cigarette smoke-induced airway inflammation through a mechanism mediated by IL-1β.