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.
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This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (#16591090).
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Yamamoto, T., Yokozeki, H. & Nishioka, K. Fas- and FasL-deficient mice are resistant to the induction of bleomycin-induced scleroderma. Arch Dermatol Res 298, 465–468 (2007). https://doi.org/10.1007/s00403-006-0712-y
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DOI: https://doi.org/10.1007/s00403-006-0712-y