Analysis of airway inflammation and remodeling induced by chronic cigarette smoke exposure in mice lungs.

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Aging and smoking are considered as major contributing factors for the development of pulmonary emphysema and airway inflammation. We utilized two mouse strains carrying intrinsic aging factor(s), senescence-accelerated mice (SAM) P1 strain and senescence marker protein-30 (SMP30) knockout (SMP30Y/-) mice. SMP30 is a multifunctional protein providing protection to cellular functions from age-associated deterioration. Both SAMP1 and SMP30Y/- mice are known as a model for senile lung since they have lungs with age-related airspace enlargement and no apparent parenchymal destruction. We evaluated in both strains cigarette smoke induced airway inflammation, emphysema, macromolecule modification by oxidative stress, and aging-related genes in the lungs. Although mice were exposed to cigarette smoke for 8 weeks, histopathological examinations did not detect any significant airway inflammation and remodeling as compared with control strains (SAMR1 and SMP30Y/+, respectively) while they did developed smoke-induced emphysema. In the lungs of SMP30Y/- mice, protein carbonyls tended to increase with aging and significantly higher than the age-matched SMP30Y/+ mice. The protein carbonyls, malondialdehyde, total glutathione, and apoptosis of lung cells were significantly increased after 8-week exposure to cigarette smoke in the SMP30Y/- mice. These results suggests that SMP30 plays important roles in regulating oxidative stress associated with aging and smoking in the lungs. In the gene expression profiles in the lungs of SAMP1, down-regulation of heat shock protein 68 gene as well as up-regulation of I1-1β and CYP2C39 genes were detected and may deserve for future investigation about their role in smoke-induce lung inflammation.