title: Gene expression profiling in mouse lung following polymeric hexamethylene diisocyanate exposure.
abstract: Isocyanates are a common cause of occupational lung disease. Hexamethylene diisocyanate (HDI), a component of polyurethane spray paints, can induce respiratory symptoms, inflammation, lung function impairment, and isocyanate asthma. The predominant form of HDI in polyurethane paints is a nonvolatile polyisocyanate known as HDI biuret trimer (HDI-BT). Exposure of mice to aerosolized HDI-BT results in pathological effects, including pulmonary edema, lung inflammation, cellular proliferation, and fibrotic lesions, which occur with distinct time courses following exposure. To identify genes that mediate lung pathology in the distinct temporal phases after exposure, gene expression profiles in HDI-BT-exposed C57BL/6J mouse lungs were analyzed. RNase protection assay (RPA) of genes involved in apoptosis, cell survival, and inflammation revealed increased expression of IkappaBalpha, Fas, Bcl-X(L), TNFalpha, KC, MIP-2, IL-6, and GM-CSF following HDI-BT exposure. Microarray analysis of approximately 10000 genes was performed on lung RNA collected from mice 6, 18, and 90 h after HDI-BT exposure and from unexposed mice. Classes of genes whose expression was increased 6 h after exposure included those involved in stress responses (particularly oxidative stress and thiol redox balance), growth arrest, apoptosis, signal transduction, and inflammation. Types of genes whose expression was increased at 18 h included proteinases, anti-proteinases, cytoskeletal molecules, and inflammatory mediators. Transcripts increased at 90 h included extracellular matrix components, transcription factors, inflammatory mediators, and cell cycle regulators. This characterization of the gene expression profile in lungs exposed to HDI-BT will provide a basis for investigating injury and repair pathways that are operative during isocyanate-induced lung disease.
authors.affiliation: Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Lee
authors.forename: Joni
authors.initials: J
authors.lastname: Ylostalo
authors.forename: Mitchell
authors.initials: M
authors.lastname: Friedman
authors.forename: Gary W
authors.initials: GW
authors.lastname: Hoyle
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003485:Cyanates / Q000378:metabolism / Q000633:toxicity*; D020869:Gene Expression Profiling / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis / Q000379:methods; D000072000:NF-KappaB Inhibitor alpha; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D000336:Aerosols; C494812:Bcl2l1 protein, mouse; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D003485:Cyanates; D020672:I-kappa B Proteins; D015850:Interleukin-6; C000606205:Nfkbia protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D019014:fas Receptor; D000072000:NF-KappaB Inhibitor alpha; C038763:hexamethylene diisocyanate trimer; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012260:Ribonucleases