Fas- and FasL-deficient mice are resistant to the induction of bleomycin-induced scleroderma

Arch Dermatol Res. 2007 Feb;298(9):465-8. doi: 10.1007/s00403-006-0712-y. Epub 2006 Nov 11.

Abstract

We have recently shown that apoptosis is induced in the lesional skin in a murine scleroderma model by local bleomycin injections, and the apoptotic pathway was mainly mediated by Fas/Fas ligand (FasL) signaling. To further investigate the involvement of apoptosis in scleroderma, we examined whether the induction of dermal sclerosis is suppressed in Fas-deficient (lpr) and FasL-deficient (gld) mice. Results of histological examination showed that the induction of dermal sclerosis by bleomycin treatment was significantly suppressed in both lpr and gld mice, in comparison with wild-type mice. The ratio of collagen contents in the bleomycin-treated skin as compared with PBS-treated skin was significantly lower in both lpr and gld mice than that in wild-type mice. The number of TUNEL-positive infiltrating cells was markedly increased following bleomycin exposure (60 +/- 11.4/HPF) in comparison with PBS treatment (9.5 +/- 6.0/HPF) in wild-type mice, which was significantly decreased in both lpr (22 +/- 4.5/HPF, P < 0.05) and gld (26 +/- 6.1/HPF, P < 0.05) mice. Our findings that lpr and gld mice were resistant to the induction of dermal sclerosis by bleomycin further suggest that Fas/FasL pathway is an important contributor involved in the pathophysiology of bleomycin-induced dermal sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic
  • Apoptosis / physiology
  • Bleomycin
  • Collagen / metabolism
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / physiology*
  • Female
  • Gene Expression Regulation
  • Immunity, Innate / genetics
  • Mice
  • Mice, Inbred C3H
  • Mice, Mutant Strains
  • Scleroderma, Systemic / chemically induced
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / physiopathology*
  • Signal Transduction / physiology
  • Skin / metabolism
  • Skin / pathology
  • fas Receptor / genetics
  • fas Receptor / physiology*

Substances

  • Antibiotics, Antineoplastic
  • Fas Ligand Protein
  • fas Receptor
  • Bleomycin
  • Collagen