First Author | Hardie WD | Year | 2002 |
Journal | Am J Respir Cell Mol Biol | Volume | 26 |
Issue | 4 | Pages | 430-7 |
PubMed ID | 11919079 | Mgi Jnum | J:133163 |
Mgi Id | MGI:3777880 | Doi | 10.1165/ajrcmb.26.4.4594 |
Citation | Hardie WD, et al. (2002) Dose-related protection from nickel-induced lung injury in transgenic mice expressing human transforming growth factor-alpha. Am J Respir Cell Mol Biol 26(4):430-7 |
abstractText | To determine the role of transforming growth factor-alpha (TGF-alpha) in protecting the lung from aerosolized nickel injury, transgenic mouse lines expressing human TGF-alpha in the pulmonary epithelium, under control of the human surfactant protein-C gene promoter, were tested. Higher expressing TGF-alpha transgenic mouse lines, expressing distinct levels of TGF-alpha, survived longer than nontransgenic control mice. Increased survival correlated with levels of TGF-alpha expression in the lung. After 72 h of nickel exposure (70 microg Ni/m3), transgenic lines with intermediate levels of the TGF-alpha expression demonstrated attenuation of lung injury. The highest expressing line (line 28) demonstrated reduced lung inflammation and edema, reduced lung wet-to-dry weight ratios, decreased bronchoalveolar lavage (BAL) protein and neutrophils, reduced interleukin (IL)-1beta, interleukin-6, and macrophage inflammatory protein-2, and maintained surfactant protein-B (SP-B) levels compared with nontransgenic controls. In the TGF-alpha transgenic mouse model, TGF-alpha protects against nickel-induced acute lung injury, at least in part, by attenuating the inflammatory response, reducing pulmonary edema, and preserving levels of SP-B. |