Physiology Department, Xiangya Medical School, Central South University, Changsha, Hunan, PR China.
Biochem Biophys Res Commun. 2010 Jun 25;397(2):290-5. doi: 10.1016/j.bbrc.2010.05.102. Epub 2010 May 26.
It is known that ozone stress can induce airway hyperresponsiveness (AHR). The underlying cellular and molecular mechanisms are not fully understood. We constructed a successive ozone-stressed rat model and showed that AHR caused by ozone stress presented as increased lung resistance (R(L)) to inhaled histamine but not baseline R(L). Meanwhile, structural disruption and decreased expression of integrin beta4 on airway epithelia were observed. Further regression analysis revealed a significant negative correlation between increases in R(L) to histamine (at 0.32 mg/ml) and mRNA expression of integrin beta4. Moreover, when integrin beta4 on human bronchial epithelial cells was knocked down, we found that reactive oxygen species was increased and apoptosis rates were higher. Overall, this study suggests that downregulation of integrin beta4 is important for the development ozone stress-induced AHR, presumably because it causes increased oxidative damage and epithelial apoptosis.
已知臭氧应激可诱导气道高反应性（AHR）。但其潜在的细胞和分子机制尚未完全阐明。我们构建了一个连续的臭氧应激大鼠模型，并表明臭氧应激引起的 AHR 表现为对吸入组织胺的肺阻力（R(L)）增加，但基础 R(L)不变。同时，观察到气道上皮整合素β4的结构破坏和表达减少。进一步的回归分析显示，R(L)对组织胺（0.32mg/ml）的增加与整合素β4的 mRNA 表达之间存在显著负相关。此外，当人支气管上皮细胞中的整合素β4被敲低时，我们发现活性氧增加，细胞凋亡率更高。总的来说，这项研究表明，整合素β4的下调对于臭氧应激诱导的 AHR 的发展很重要，可能是因为它导致氧化损伤和上皮细胞凋亡增加。
