Abstract
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 (ΔN23-KGF) protects against acute lung injury. The present study investigated whether or not ΔN23-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 ΔN23-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. ΔN23-KGF prevented NA-induced airflow limitation and Clara cell permeability, and resulted in twice as many Clara cells compared with PBS pre-treatment. ΔN23-KGF-pre-treated mice exhibited increased expression of proliferating cell nuclear antigen mRNA. Cytochrome P450 isoform 2F2, which converts NA into its toxic metabolite, was reduced by ∼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. Copyright
Original language | English (US) |
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Pages (from-to) | 694-704 |
Number of pages | 11 |
Journal | European Respiratory Journal |
Volume | 32 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2008 |
Keywords
- Airway epithelial injury
- Cytochrome P
- Keratinocyte growth factor
- Naphthalene
- Secretoglobin
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Medicine(all)