• Am. J. Respir. Cell Mol. Biol. · Apr 2002

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

    • William D Hardie, Daniel R Prows, Alyssa Piljan-Gentle, Michelle R Dunlavy, Scott C Wesselkamper, George D Leikauf, and Thomas R Korfhagen.
    • Division of Pulmonary Medicine, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. bill.hardie@chmcc.org
    • Am. J. Respir. Cell Mol. Biol. 2002 Apr 1; 26 (4): 430-7.

    AbstractTo 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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