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Publication : Dose-related protection from nickel-induced lung injury in transgenic mice expressing human transforming growth factor-alpha.

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.
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