一氧化氮与气道上皮屏障功能：紧密连接蛋白及上皮通透性的调节
Nitric oxide and airway epithelial barrier function: regulation of tight junction proteins and epithelial permeability.
作者信息
Olson Nels, Greul Anne-Katrin, Hristova Milena, Bove Peter F, Kasahara David I, van der Vliet Albert
机构信息
Department of Pathology, College of Medicine, University of Vermont, D205 Given Building, 89 Beaumont Avenue, Burlington VT 05405, USA.
出版信息
Arch Biochem Biophys. 2009 Apr 15;484(2):205-13. doi: 10.1016/j.abb.2008.11.027. Epub 2008 Dec 10.
Acute airway inflammation is associated with enhanced production of nitric oxide (NO(.)) and altered airway epithelial barrier function, suggesting a role of NO(.) or its metabolites in epithelial permeability. While high concentrations of S-nitrosothiols disrupted transepithelial resistance (TER) and increased permeability in 16HBE14o- cells, no significant barrier disruption was observed by NONOates, in spite of altered distribution and expression of some TJ proteins. Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response to inflammatory cytokines was independent of NOS2, based on similar effects in MTE cells from NOS2-/- mice and a lack of effect of the NOS2-inhibitor 1400W. Cell pre-incubation with LPS protected MTE cells from TER loss and increased permeability by H2O2, which was independent of NOS2. However, NOS2 was found to contribute to epithelial wound repair and TER recovery after mechanical injury. Overall, our results demonstrate that epithelial NOS2 is not responsible for epithelial barrier dysfunction during inflammation, but may contribute to restoration of epithelial integrity.
急性气道炎症与一氧化氮（NO(.)）生成增加及气道上皮屏障功能改变有关，提示NO(.)或其代谢产物在上皮通透性方面发挥作用。虽然高浓度的S-亚硝基硫醇会破坏16HBE14o-细胞的跨上皮电阻（TER）并增加通透性，但尽管一些紧密连接（TJ）蛋白的分布和表达发生了改变，NONOates并未观察到明显的屏障破坏。基于来自NOS2-/-小鼠的MTE细胞有类似效应以及NOS2抑制剂1400W无效，炎症细胞因子对小鼠气管上皮（MTE）细胞单层的屏障破坏与NOS2无关。用脂多糖（LPS）预孵育细胞可保护MTE细胞免受TER损失，并防止H2O2导致的通透性增加，这与NOS2无关。然而，发现NOS2有助于机械损伤后上皮伤口修复和TER恢复。总体而言，我们的结果表明，上皮NOS2在炎症期间并非上皮屏障功能障碍的原因，但可能有助于上皮完整性的恢复。
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