Am. J. Respir. Cell Mol. Biol., Volume 23, Number 4, October, 2000 466-474

Differential Gene Expression in the Initiation and Progression of Nickel-Induced Acute Lung Injury

Susan A. McDowell, Kelly Gammon, Cindy J. Bachurski, Jonathan S. Wiest, John E. Leikauf, Daniel R. Prows, and George D. Leikauf

Departments of Environmental Health, Molecular and Cellular Physiology, and Medicine, University of Cincinnati, Cincinnati; and Information Services and Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio

Acute lung injury, an often fatal condition, can result from a wide range of insults leading to a complex series of biologic responses. Despite extensive research, questions remain about the interplay of the factors involved and their role in acute lung injury. We proposed that assessing the temporal and functional relationships of differentially expressed genes after pulmonary insult would reveal novel interactions in the progression of acute lung injury. Specifically, 8,734 sequence-verified murine complementary DNAs were analyzed in mice throughout the initiation and progression of acute lung injury induced by particulate nickel sulfate. This study revealed the expression patterns of genes previously associated with acute lung injury in relationship to one another and also uncovered changes in expression of a number of genes not previously associated with acute lung injury. The overall pattern of gene expression was consistent with oxidative stress, hypoxia, cell proliferation, and extracellular matrix repair, followed by a marked decrease in pulmonary surfactant proteins. Also, expressed sequence tags (ESTs), with nominal homology to known genes, displayed similar expression patterns to those of known genes, suggesting possible roles for these ESTs in the pulmonary response to injury. Thus, this analysis of the progression and response to acute lung injury revealed novel gene expression patterns.

This article has been cited by other articles:

				K. Bein, S. C. Wesselkamper, X. Liu, M. Dietsch, N. Majumder, V. J. Concel, M. Medvedovic, M. A. Sartor, L. N. Henning, C. Venditto, et al. Surfactant-Associated Protein B Is Critical to Survival in Nickel-Induced Injury in Mice Am. J. Respir. Cell Mol. Biol., August 1, 2009; 41(2): 226 - 236. [Abstract] [Full Text] [PDF]

				A. A. Nemec, G. D. Leikauf, B. R. Pitt, K. J. Wasserloos, and A. Barchowsky Nickel Mobilizes Intracellular Zinc to Induce Metallothionein in Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., July 1, 2009; 41(1): 69 - 75. [Abstract] [Full Text] [PDF]

				J. J. Reece, M. C. Siracusa, and A. L. Scott Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively Activated Alveolar Macrophages Infect. Immun., September 1, 2006; 74(9): 4970 - 4981. [Abstract] [Full Text] [PDF]

				A. Mallakin, L. W. Kutcher, S. A. McDowell, S. Kong, R. Schuster, A. B. Lentsch, B. J. Aronow, G. D. Leikauf, and S. E. Waltz Gene Expression Profiles of Mst1r-Deficient Mice during Nickel-Induced Acute Lung Injury Am. J. Respir. Cell Mol. Biol., January 1, 2006; 34(1): 15 - 27. [Abstract] [Full Text] [PDF]

				S. C. Wesselkamper, S. A. McDowell, M. Medvedovic, T. P. Dalton, H. S. Deshmukh, M. A. Sartor, L. M. Case, L. N. Henning, M. T. Borchers, C. R. Tomlinson, et al. The Role of Metallothionein in the Pathogenesis of Acute Lung Injury Am. J. Respir. Cell Mol. Biol., January 1, 2006; 34(1): 73 - 82. [Abstract] [Full Text] [PDF]

				S. C. Wesselkamper, L. M. Case, L. N. Henning, M. T. Borchers, J. W. Tichelaar, J. M. Mason, N. Dragin, M. Medvedovic, M. A. Sartor, C. R. Tomlinson, et al. Gene Expression Changes during the Development of Acute Lung Injury Role of Transforming Growth Factor {beta} Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1399 - 1411. [Abstract] [Full Text] [PDF]

				J. A. Whitsett, C. J. Bachurski, K. C. Barnes, P. A. Bunn Jr., L. M. Case, D. N. Cook, D. Crooks, M. W. Duncan, L. Dwyer-Nield, R. C. Elston, et al. Functional Genomics of Lung Disease Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2/S1): S1 - S81. [Full Text] [PDF]

				S. Perkowski, J. Sun, S. Singhal, J. Santiago, G. D. Leikauf, and S. M. Albelda Gene Expression Profiling of the Early Pulmonary Response to Hyperoxia in Mice Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 682 - 696. [Abstract] [Full Text] [PDF]

				S. A. McDowell, K. Gammon, B. Zingarelli, C. J. Bachurski, B. J. Aronow, D. R. Prows, and G. D. Leikauf Inhibition of Nitric Oxide Restores Surfactant Gene Expression following Nickel-Induced Acute Lung Injury Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 188 - 198. [Abstract] [Full Text] [PDF]

				W. D. Hardie, D. R. Prows, A. Piljan-Gentle, M. R. Dunlavy, S. C. Wesselkamper, G. D. Leikauf, and T. R. Korfhagen Dose-Related Protection from Nickel-Induced Lung Injury in Transgenic Mice Expressing Human Transforming Growth Factor-alpha Am. J. Respir. Cell Mol. Biol., April 1, 2002; 26(4): 430 - 437. [Abstract] [Full Text] [PDF]

				G. D. Leikauf, S. A. McDowell, S. C. Wesselkamper, W. D. Hardie, J. E. Leikauf, T. R. Korfhagen, and D. R. Prows Acute Lung Injury : Functional Genomics and Genetic Susceptibility Chest, March 1, 2002; 121 (2009): 70S - 75S. [Abstract] [Full Text] [PDF]

				S. A. McDowell, A. Mallakin, C. J. Bachurski, K. Toney-Earley, D. R. Prows, T. Bruno, K. H. Kaestner, D. P. Witte, H. Melin-Aldana, S. J. F. Degen, et al. The Role of the Receptor Tyrosine Kinase Ron in Nickel-Induced Acute Lung Injury Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 99 - 104. [Abstract] [Full Text] [PDF]

				D. R. Prows and G. D. Leikauf Quantitative Trait Analysis of Nickel-Induced Acute Lung Injury in Mice Am. J. Respir. Cell Mol. Biol., June 1, 2001; 24(6): 740 - 746. [Abstract] [Full Text] [PDF]