Keratinocyte growth factor protects against Clara cell injury induced by naphthalene
| Autor: | Ali Oender Yildirim, Heinz Fehrenbach, P. Kilb, Bernd Müller, Martina Veith, T. Rausch, L. S. Van Winkle |
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| Rok vydání: | 2008 |
| Předmět: |
Pulmonary and Respiratory Medicine
Gene isoform Pathology medicine.medical_specialty Fibroblast Growth Factor 7 Acute Lung Injury Naphthalenes Lung injury Article law.invention Mice chemistry.chemical_compound Cytochrome P-450 Enzyme System law Gene expression medicine Animals Bronchioles Plethysmography Whole Body Messenger RNA biology Epithelial Cells respiratory system Molecular biology Recombinant Proteins respiratory tract diseases Proliferating cell nuclear antigen Disease Models Animal chemistry Recombinant DNA biology.protein Keratinocyte growth factor |
| Zdroj: | European Respiratory Journal. 32:694-704 |
| ISSN: | 1399-3003 0903-1936 |
| DOI: | 10.1183/09031936.00155107 |
| Popis: | Airway epithelial cells are exposed to environmental toxicants that result in airway injury. Naphthalene (NA) causes site-selective damage to Clara cells in mouse distal airways. N-terminally truncated recombinant human keratinocyte growth factor (DeltaN23-KGF) protects against acute lung injury. The present study investigated whether or not DeltaN23-KGF protects against NA-induced acute Clara cell damage by measuring airway responses specifically and in order to identify underlying molecular mechanisms. Mice were treated with DeltaN23-KGF or PBS 33 h prior to injection of 200 mg.kg body weight(-1) NA. Lung function was analysed by head-out body plethysmography. Distal airways isolated by microdissection were assessed for cell permeability using ethidium homodimer-1. Immunohistochemistry of Clara cell-specific protein in conjunction with a physical dissector was used to quantify Clara cell numbers. RNA was isolated from frozen airways in order to analyse gene expression using quantitative RT-PCR. DeltaN23-KGF prevented NA-induced airflow limitation and Clara cell permeability, and resulted in twice as many Clara cells compared with PBS pre-treatment. DeltaN23-KGF-pre-treated mice exhibited increased expression of proliferating cell nuclear antigen mRNA. Cytochrome P(450) isoform 2F2, which converts NA into its toxic metabolite, was reduced by approximately 50%. The present results demonstrate that pre-treatment with N-terminally truncated recombinant human keratinocyte growth factor protects against naphthalene-induced injury. This suggests that N-terminally truncated recombinant human keratinocyte growth factor exerts its beneficial effect through a decrease in the expression of cytochrome P(450) isoform 2F2. |
| Databáze: | OpenAIRE |
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