Lee Hyeon-Soo, Wang Yulian, Maciejewski Benjamin S, Esho Kenny, Fulton Christiaan, Sharma Surendra, Sanchez-Esteban Juan
Department of Pediatrics, Women & Infants Hospital of Rhode Island, 101 Dudley Street, Providence, RI 02905, USA.
Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L225-32. doi: 10.1152/ajplung.00370.2007. Epub 2007 Dec 7.
Mechanical ventilation plays a central role in the pathogenesis of bronchopulmonary dysplasia. However, the mechanisms by which excessive stretch of fetal or neonatal type II epithelial cells contributes to lung injury are not well defined. In these investigations, isolated embryonic day 19 fetal rat type II epithelial cells were cultured on substrates coated with fibronectin and exposed to 5% or 20% cyclic stretch to simulate mechanical forces during lung development or lung injury, respectively. Twenty percent stretch of fetal type II epithelial cells increased necrosis, apoptosis, and proliferation compared with control, unstretched samples. By ELISA and real-time PCR (qRT-PCR), 20% stretch increased secretion of IL-8 into the media and IL-8 gene expression and inhibited IL-10 release. Interestingly, administration of recombinant IL-10 before 20% stretch did not affect cell lysis but significantly reduced apoptosis and IL-8 release compared with stretched samples without IL-10. Collectively, our studies suggest that IL-10 may play an important role in protection of fetal type II epithelial cells from injury secondary to stretch.
机械通气在支气管肺发育不良的发病机制中起核心作用。然而，胎儿或新生儿II型上皮细胞过度拉伸导致肺损伤的机制尚未明确。在这些研究中，将分离的胚胎第19天胎鼠II型上皮细胞培养在涂有纤连蛋白的基质上，并分别暴露于5%或20%的周期性拉伸，以模拟肺发育或肺损伤期间的机械力。与未拉伸的对照样本相比，胎儿II型上皮细胞20%的拉伸增加了坏死、凋亡和增殖。通过酶联免疫吸附测定（ELISA）和实时定量聚合酶链反应（qRT-PCR），20%的拉伸增加了培养基中白细胞介素-8（IL-8）的分泌和IL-8基因表达，并抑制了白细胞介素-10（IL-10）的释放。有趣的是，在20%拉伸前给予重组IL-10对细胞裂解没有影响，但与未给予IL-10的拉伸样本相比，显著降低了凋亡和IL-8释放。总体而言，我们的研究表明，IL-10可能在保护胎儿II型上皮细胞免受拉伸继发损伤方面发挥重要作用。
