Genetic control of apoptosis in developing pulmonary fibrosis

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Upregulation of Fas and FasL expression in bronchiolar and alveolar epithelial cells Was found in patients with pulmonary fibrosis. In Bleomycin-treated experimental animal, apoptosis in lung tissue through the interaction of Fas-FasL contributes to development of pulmonary fibrosis. Fag are cell surface molecules that trigger apoptosis or inflammation upon engagement by specific receptor or antibody. FADD is recruited to the cytoplasmic domain of these receptors upon their activation and works as common mediator to induce apoptosis. Based upon these knowledge, we hypothesized that intracellular signals through Fas modified to be dominant-negative signal would suppress the development of pulmonary fibrosis. Tb evaluate this hypothesis, we constructed recombinant adenovirus vector coding FADD deletion mutant lacking the death effector domain. Bleomycin-induced pulmonary fibrosis was partially ameliorated by intratracheal FADD dominant negative transduction. This result would provide the basis for a novel therapeutic modality in pulmonary fibrosis.