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

23 Citations (Scopus)

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

Fibroblast Growth Factor 7
Wounds and Injuries
Cytochrome P-450 Enzyme System
Permeability
Protein Isoforms
Uteroglobin
Microdissection
Plethysmography
Acute Lung Injury
Poisons
Proliferating Cell Nuclear Antigen
naphthalene
Cell Count
Epithelial Cells
Immunohistochemistry
Head
Body Weight
RNA
Gene Expression
Polymerase Chain Reaction

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

Keratinocyte growth factor protects against Clara cell injury induced by naphthalene. / Yildirim, A. Ö; Veith, M.; Rausch, T.; Müller, B.; Kilb, P.; Van Winkle, L. S.; Fehrenbach, H.

In: European Respiratory Journal, Vol. 32, No. 3, 09.2008, p. 694-704.

Research output: Contribution to journalArticle

Yildirim, AÖ, Veith, M, Rausch, T, Müller, B, Kilb, P, Van Winkle, LS & Fehrenbach, H 2008, 'Keratinocyte growth factor protects against Clara cell injury induced by naphthalene', European Respiratory Journal, vol. 32, no. 3, pp. 694-704. https://doi.org/10.1183/09031936.00155107
Yildirim, A. Ö ; Veith, M. ; Rausch, T. ; Müller, B. ; Kilb, P. ; Van Winkle, L. S. ; Fehrenbach, H. / Keratinocyte growth factor protects against Clara cell injury induced by naphthalene. In: European Respiratory Journal. 2008 ; Vol. 32, No. 3. pp. 694-704.
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