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Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin
Published on: April 30, 2019
Fas- and FasL-deficient mice are resistant to the induction of bleomycin-induced scleroderma
Toshiyuki Yamamoto1, Hiroo Yokozeki, Kiyoshi Nishioka
1Department of Dermatology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan. toyamade@tokyo-med.ac.jp
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.
Insights
The Fas/Fas ligand pathway is crucial in bleomycin-induced scleroderma. Mice lacking Fas or Fas ligand showed reduced skin thickening and collagen, indicating this pathway
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Apoptosis (programmed cell death) is induced in murine scleroderma skin lesions by bleomycin.
- The Fas/Fas ligand (FasL) signaling pathway is the primary mediator of this apoptosis.
Purpose of the Study:
- To investigate the role of apoptosis in scleroderma pathogenesis.
- To determine if dermal sclerosis induction is suppressed in mice deficient in Fas or FasL.
Main Methods:
- Histological examination of skin lesions in bleomycin-treated wild-type, Fas-deficient (lpr), and FasL-deficient (gld) mice.
- Quantification of collagen content in skin samples.
- Assessment of TUNEL-positive infiltrating cells to measure apoptosis.
Main Results:
- Bleomycin-induced dermal sclerosis was significantly suppressed in lpr and gld mice compared to wild-type mice.
- Collagen content was significantly lower in bleomycin-treated skin of lpr and gld mice.
- The number of apoptotic infiltrating cells (TUNEL-positive) was significantly reduced in lpr and gld mice.
Conclusions:
- Fas-deficient (lpr) and FasL-deficient (gld) mice are resistant to bleomycin-induced dermal sclerosis.
- The Fas/FasL pathway is a significant contributor to the pathophysiology of bleomycin-induced dermal sclerosis.
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