Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis

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Abstract

The Fas ligand is predominantly expressed in activated T lymphocytes and is one of the major effector molecules of cytotoxic T lymphocytes and natural killer cells. Previously, we found excessive apoptosis of epithelial cells and infiltrating lymphocytes expressing Fas ligand mRNA in the lung tissue of bleomycin-induced pulmonary fibrosis in mice. Here we demonstrated that the administration of a soluble form of Fas antigen or anti-Fas ligand antibody prevented the development of this model and that lpr and gld mice were resistant against the induction of pneumopathy. These results suggest that the Fas-Fas ligand pathway plays an essential role in the development of pulmonary fibrosis and that preventing this pathway could have therapeutic value in lung injury and fibrosis.

Authors

Kazuyoshi Kuwano, Naoki Hagimoto, Masayuki Kawasaki, Takehiro Yatomi, Norio Nakamura, Shigekazu Nagata, Takashi Suda, Ritsuko Kunitake, Takashige Maeyama, Hiroyuki Miyazaki, Nobuyuki Hara