Involvement of IL-13 in tobacco smoke-induced changes in the structure and function of rat intrapulmonary airways.
Chronic obstructive pulmonary disease (COPD) involves disease of small airways with an increase in airway smooth muscle sensitivity to spasmogens and with structural changes described as airway remodeling. We investigated the effect of tobacco smoke (TS) exposure on the structure and function of small airways in rats and the role of IL-13 in this response. Precision-cut lung slices (230-280 microm) were prepared from male Sprague-Dawley rats after acute (3 d) or chronic (8 or 16 wk) daily exposure to TS or air. Carbachol (CCh) and 5-hydroxytryptamine (5HT) concentration responses were performed on airways (50-400 microm diameter). The effect of IL-13 in vitro on small airway sensitivity to CCh and 5HT was also determined. Acute exposure to TS did not affect the sensitivity of the intrapulmonary airways to either spasmogen. After 8 weeks of TS exposure, airway hyperresponsiveness (AHR) to CCh was evident (log EC(50) CCh: air = 0.22 microM; TS = -0.12 microM; P = 0.019); AHR to 5HT was also observed after the 16-week exposure to TS (air = -0.85 microM; TS = -1.06 microM; P = 0.038). Chronic TS exposure increased airway wall SMA content, which correlated with increased expression of IL-13 and transforming growth factor (TGF)-beta(1) in the lung tissues. In vitro incubation with IL-13, but not TGF-beta(1), induced changes in small airway sensitivity to CCh and 5HT. Chronic TS exposure induces increased responsiveness in intrapulmonary airways of rats that may be mediated in part by an increase in IL-13.
Cooper
Philip R
PR
Section of Airway Disease, National Heart and Lung Institute, London. UK. CooperP@mail.med.upenn.edu
Poll
Christopher T
CT
Barnes
Peter J
PJ
Sturton
R Graham
RG
D000199:Actins / Q000378:metabolism; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D003094:Collagen / Q000737:chemistry; D004195:Disease Models, Animal; D018793:Interleukin-13 / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000199:Actins; D018793:Interleukin-13; D012906:Smoke; D053773:Transforming Growth Factor beta1; D003094:Collagen