Attenuation of bleomycin-induced pneumopathy in mice by a caspase inhibitor.
Kuwano, Kazuyoshi, Ritsuko Kunitake, Takashige Maeyama, Naoki Hagimoto,
Masayuki Kawasaki, Tokuji Matsuba, Michihiro Yoshimi, Ichiro Inoshima, Koichiro
Yoshida, and Nobuyuki Hara.
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences,
Kyushu University, Higashiku, Fukuoka 812«hyphen»8582, Japan
APStracts 7:0251L, 2000.
Caspases have been implicated in the effector process of apoptosis in several systems
including the Fas-Fas ligand pathway. We previously demonstrated that excessive
apoptosis of lung epithelial cells and the Fas-FasL pathway were essential in the
pathogenesis of bleomycin-induced pneumopathy in mice. Therefore, the purpose of this
study was to investigate whether a caspase inhibitor could prevent the development of
this model. The expression of caspase-1 and caspase-3 was upregulated on lung epithelial
cells, alveolar macrophages, and infiltrating inflammatory cells in this model. We
demonstrated that a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-
Asp fluoromethylketone, decreased the caspase-1- and caspase-3-like activity, the
number of apoptotic cells, the pathological grade of lung inflammation and fibrosis, and
the hydroxyproline content in lung tissues in this model. We conclude that caspase
inhibitors could be a new therapeutic approach against lung injury and pulmonary
fibrosis.
Received 11 February 2000; accepted in final form 19 September 2000
APS Manuscript Number L20-0.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 7 November 2000