Retinoic acid inhibits elastase-induced injury in human lung epithelial cell lines.
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.
Nakajoh
Mizue
M
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan.
Fukushima
Takeyasu
T
Suzuki
Tomoko
T
Yamaya
Mutsuo
M
Nakayama
Katsutoshi
K
Sekizawa
Kiyohisa
K
Sasaki
Hidetada
H
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*
D014212:Tretinoin; D010196:Pancreatic Elastase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases