Reduced tumor necrosis factor-alpha and transforming growth factor-beta(1)expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure

Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta mRNA and protein expression and the degree of fibroproliferative response to inhaled asbestos fibers are clearly reduced in the 129 inbred mouse stra in as compared with typical fibrogenesis observed in the C57BL/6 Inbred str ain. The C57BL/6 mice showed prominent lesions at bronchiolar-alveolar duct (BAD) junctions where asbestos fibers deposit and responding macrophages a ccumulate. The 129 mice, however, were generally indistinguishable from con trols even though the numbers of asbestos fibers deposited in the lungs of all exposed animals were the same, Quantitative morphometry of H&E-stained lung sections comparing the C57BL/G and 129 mice showed significantly less mean cross-sectional area of the BAD junctions in the 129 animals, apparent at both 48 hours and 4 weeks after exposure. In addition, fewer macrophage s had accumulated at these sites In the 129 mice. Nuclear bromodeoxyuridine immunostaining demonstrated that the number of proliferating cells at firs t alveolar duct bifurcations and In adjacent terminal bronchioles was signi ficantly reduced in the 129 strain compared with C57BL/6 mice at 48 hours a fter exposure (P < 0.01), TNF-alpha and TGF-beta(1) gene expression, as mea sured by in situ hybridization, was reduced In the 129 mice at 48 hours aft er exposure, and expression of TNF-alpha and TGF-beta(1) protein, as measur ed by immunohistochemistry, was similarly reduced or absent in the 129 anim als. We postulate that the protection afforded the 129 mice is related to r eduction of growth factor expression by the bronchiolar-alveolar epithelium and lung macrophages.