Effects of corticosteroid-induced apoptosis on airway epithelial wound closure in vitro
Effects of corticosteroid-induced apoptosis on airway epithelial wound closure in vitro
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DOI：
10.1152/ajplung.00322.2005
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发表时间：
2006-10-01
影响因子：
4.9
通讯作者：
White, Steven R.
中科院分区：
文献类型：
--
作者：
Dorscheid, Delbert R.;Patchell, Benjamin J.;White, Steven R.
激素诱导的细胞凋亡对气道上皮创伤愈合的影响。美国生理学杂志肺细胞分子生理学291：L794-L 801，2006年。首次出版于2006年6月2日; doi：10.1152/ajplung。00322.2005.气道上皮损伤在哮喘中很常见。皮质类固醇诱导培养的气道上皮细胞凋亡并抑制其增殖。细胞凋亡是否有助于损伤后受损的上皮细胞修复尚不清楚。我们在伤口闭合的体外模型中研究了皮质类固醇是否会损害上皮细胞迁移。在培养的1HAEo（-）人气道上皮细胞单层中创建伤口（类似于0.5-1.3 mm（2）），然后用高达10 μ M地塞米松或布地奈德处理细胞24小时。用地塞米松预处理细胞24或48 h，观察长期暴露对伤口愈合的影响。12小时后，用10 μ M地塞米松预处理48小时的单层的剩余伤口面积为43 +/- 18%，而未处理的对照单层为10 +/- 8%。损伤后立即添加皮质类固醇并没有显著减缓闭合。12小时后，用10 μ M布地奈德处理的单层的剩余伤口面积为39 +/- 4%，而未处理的对照单层为43 +/- 3%。通过末端脱氧核苷酸转移酶介导的dUTP生物素缺口末端标记法在伤口边缘和远离伤口边缘处测量的凋亡上皮细胞的比例在用布地奈德治疗的单层中高于对照组。而地塞米松处理后，耐药的1HAEo（-）.Bcl-2（+）细胞系的伤口闭合无明显变化。我们证明，皮质类固醇治疗机械损伤前损害气道上皮细胞迁移。损伤后添加皮质类固醇不会减缓迁移，尽管它们能够诱导这些细胞的凋亡。
Effects of corticosteroid-induced apoptosis on airway epithelial wound closure in vitro. Am J Physiol Lung Cell Mol Physiol 291: L794-L801, 2006. First published June 2, 2006; doi: 10.1152/ajplung. 00322.2005. Damage to the airway epithelium is common in asthma. Corticosteroids induce apoptosis in and suppress proliferation of airway epithelial cells in culture. Whether apoptosis contributes to impaired epithelial cell repair after injury is not known. We examined whether corticosteroids would impair epithelial cell migration in an in vitro model of wound closure. Wounds (similar to 0.5-1.3 mm(2)) were created in cultured 1HAEo(-) human airway epithelial cell monolayers, after which cells were treated with up to 10 mu M dexamethasone or budesonide for 24 h. Cultured cells were pretreated for 24 or 48 h with dexamethasone to observe the effect of long-term exposure on wound closure. After 12 h, the remaining wound area in monolayers pretreated for 48 h with 10 mu M dexamethasone was 43 +/- 18% vs. 10 +/- 8% for untreated control monolayers. The addition of either corticosteroid immediately after injury did not slow closure significantly. After 12 h the remaining wound area in monolayers treated with 10 mu M budesonide was 39 +/- 4% vs. 43 +/- 3% for untreated control monolayers. The proportion of apoptotic epithelial cells as measured by terminal deoxynucleotidyltransferase-mediated dUTP biotin nick end labeling both at and away from the wound edge was higher in monolayers treated with budesonide compared with controls. However, wound closure in the apoptosis-resistant 1HAEo(-).Bcl-2(+) cell line was not different after dexamethasone treatment. We demonstrate that corticosteroid treatment before mechanical wounding impairs airway epithelial cell migration. The addition of corticosteroids after injury does not slow migration, despite their ability to induce apoptosis in these cells.