title: Retinoic acid inhibits elastase-induced injury in human lung epithelial cell lines.
abstract: 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.
authors.affiliation: Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Mizue
authors.initials: M
authors.lastname: Nakajoh
authors.forename: Takeyasu
authors.initials: T
authors.lastname: Fukushima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nakayama
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Sekizawa
authors.forename: Hidetada
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D014212:Tretinoin; D010196:Pancreatic Elastase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases