Increased expression of iNOS and c-fos via regulation of protein tyrosine phosphorylation and MEK1/ERK2 proteins in terminal bronchiole lesions in the lungs of rats exposed to cigarette smoke

Epidemiological evidence suggests that smoking is a major cause of human lu ng cancer. However, the mechanism by which cigarette smoke induces the canc er remains unestablished. To evaluate the effects of cigarette smoke on the expression of inducible nitric oxide synthase (iNOS), nuclear protooncogen es and related mitogen-activated protein kinases (MAPKs) in rat lung tissue , a histopathological study of the effects of gasphase cigarette smoke on r at lung tissue were carried out. The terminal bronchioles were found to be infiltrated predominantly by lymphocytes in the peribronchiolar region and a mild to moderate degree of emphysema was noted in the alveolar spaces. Th e terminal bronchioles also showed marked lipid peroxidation, dilatation. a nd peribronchiolar fibrosis. Immunohistochemical evaluation showed that the expression of iNOS, NF-kappaB, MAPKs (MEK1, ERK2), phosphotyrosine protein and c-fos was increased in the terminal bronchioles but protein kinase C ( PKC), MEKK-1, c-jun, p38 and c-myc showed no change. These results provide evidence to suggest that exposure to cigarette smoke results in oxidant str ess which leads to the stimulation of iNOS and c-fos together with the indu ction of protein tyrosine phosphorylation and MEK1/ERK2 which in turn may p romote lung pathogenesis.