Keratinocyte growth factor protects against Clara cell injury induced by naphthalene

A. Ö Yildirim, M. Veith, T. Rausch, B. Müller, P. Kilb, L. S. Van Winkle, H. Fehrenbach

Research output: Contribution to journalArticle

24 Scopus citations

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 languageEnglish (US)
Pages (from-to)694-704
Number of pages11
JournalEuropean Respiratory Journal
Volume32
Issue number3
DOIs
StatePublished - Sep 2008

    Fingerprint

Keywords

  • Airway epithelial injury
  • Cytochrome P
  • Keratinocyte growth factor
  • Naphthalene
  • Secretoglobin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

Yildirim, A. Ö., Veith, M., Rausch, T., Müller, B., Kilb, P., Van Winkle, L. S., & Fehrenbach, H. (2008). Keratinocyte growth factor protects against Clara cell injury induced by naphthalene. European Respiratory Journal, 32(3), 694-704. https://doi.org/10.1183/09031936.00155107