Retinoic acid inhibits elastase-induced injury in human lung epithelial cell lines
Retinoic acid inhibits elastase-induced injury in human lung epithelial cell lines
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DOI：
10.1165/rcmb.4845
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发表时间：
2003-03-01
影响因子：
6.4
通讯作者：
Sasaki, H
中科院分区：
文献类型：
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作者：
Nakajoh, M;Fukushima, T;Sasaki, H
使用从人脓痰中提取的弹性蛋白酶、BEAS-2B人支气管上皮细胞系、A549人II型肺细胞系以及人气管上皮细胞的原代培养物，研究了视黄酸对弹性蛋白酶诱导的肺上皮细胞损伤的保护作用。弹性蛋白酶以浓度和时间依赖性方式降低 BEAS-2B 细胞、A549 细胞和人气管上皮细胞的活力。弹性蛋白酶还诱导BEAS-2B细胞、A549细胞和气管上皮细胞凋亡，通过细胞死亡检测酶联免疫吸附试验和末端脱氧核糖核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）方法检测到。单独的视黄酸不影响BEAS-2B细胞、A549细胞或气管上皮细胞的活力，并且不诱导细胞凋亡。然而，视黄酸可防止弹性蛋白酶诱导的BEAS-2B细胞、A549细胞和气管上皮细胞的活力下降并减少细胞凋亡。同样，视黄酸抑制弹性蛋白酶诱导的 BEAS-2B 细胞和 A549 细胞中的 caspase 3 活性以及弹性蛋白酶的蛋白水解活性。此外，Caspase 3抑制剂抑制弹性蛋白酶诱导的细胞凋亡。这些发现表明，视黄酸可能部分通过抑制弹性蛋白酶的蛋白水解活性和通过弹性蛋白酶抑制 caspase 3 活性来抑制弹性蛋白酶诱导的肺上皮细胞损伤。因此，视黄酸可能对弹性蛋白酶诱导的肺损伤和随后的肺气肿的发展具有保护作用。
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.