© 2003 American Thoracic Society DOI: 10.1165/rcmb.4845 Retinoic Acid Inhibits Elastase-Induced Injury in Human Lung Epithelial Cell LinesDepartment of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai; and Department of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan Address correspondence to: Hidetada Sasaki, M.D., Professor and Chairman, Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan. E-mail: dept{at}geriat.med.tohoku.ac.jp The protective effects of retinoic acid on elastase-induced lung epithelial cell injury were studied using elastase extracted from purulent human sputum, the BEAS-2B human bronchial epithelial cell line, A549 human type II lung cell line, and primary cultures of human tracheal epithelial cells. Elastase decreased viability of BEAS-2B cells, A549 cells, and human tracheal epithelial cells in concentration- and time-dependent fashions. Elastase also induced apoptosis of BEAS-2B cells, A549 cells, and the tracheal epithelial cells detected with cell death detection enzyme-linked immunosorbent assay and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) methods. Retinoic acid alone did not affect the viability of BEAS-2B cells, A549 cells, or the tracheal epithelial cells, and did not induce apoptosis of the cells. However, retinoic acid prevented the decreases in the viability and reduced apoptosis of BEAS-2B cells, A549 cells, and the tracheal epithelial cells induced by elastase. Likewise, retinoic acid inhibited caspase 3 activity in BEAS-2B cells and A549 cells induced by elastase, as well as proteolytic activity of elastase. Furthermore, caspase 3 inhibitor inhibited the elastase-induced apoptosis of the cells. These findings suggest that retinoic acid may inhibit elastase-induced lung epithelial cell injury partly through the inhibition of proteolytic activity of elastase and through the inhibition of caspase 3 activity by elastase. Retinoic acid may, therefore, have protective effects against the elastase-induced lung injury and subsequent development of pulmonary emphysema.
Abbreviations: Dulbecco's modified Eagle's medium, DMEM • dimethyl sulfoxide, DMSO • enzyme-linked immunosorbent assay, ELISA • fetal calf serum, FCS • human tracheal epithelial cells, HTE cells • phosphate-buffered saline, PBS • terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling, TUNEL This article has been cited by other articles:
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