Abstract：
The genital epithelial barrier is a crucial first line of defence against HIV, and epithelial disruption may enhance HIV susceptibility. Assessment of genital epithelial integrity requires biopsies, but their collection is not practical in many research settings. A validated biomarker of genital epithelial barrier integrity would therefore be useful. The purpose of this study was to evaluate soluble E-cadherin (sE-cad) as a marker of genital epithelial disruption.
Using in vitro models of endocervical and foreskin epithelial cells, we assessed changes in sE-cad, IL-6, IL-1β, and IL-1α levels following mechanical disruption. We also assessed changes in sE-cad levels in vivo in cervicovaginal secretions after epithelial disruption by endocervical cytobrush sampling in Canadian women, and assessed the relationship between levels of sE-cad in coronal sulcus swabs to membrane-bound E-cadherin in the overlying foreskin tissue in Ugandan men.
sE-cad levels immediately increased after in vitro epithelial physical disruption with the degree of elevation dependent on the extent of disruption, as did levels of IL-1β and IL-1α; this was followed by a delayed increase in IL-6 levels. In vivo results confirmed that sE-cad levels in cervicovaginal secretions were elevated 6 h after cytobrush sampling when compared to baseline. Furthermore, levels of sE-cad in the prepuce were inversely correlated with the amount of membrane-bound E-cadherin of overlying tissue.
Our results validate the use of sE-cad as a marker of epithelial disruption and demonstrate that the processes of physical disruption and inflammation in the genital tract are strongly intertwined.
Using in vitro models of endocervical and foreskin epithelial cells, we assessed changes in sE-cad, IL-6, IL-1β, and IL-1α levels following mechanical disruption. We also assessed changes in sE-cad levels in vivo in cervicovaginal secretions after epithelial disruption by endocervical cytobrush sampling in Canadian women, and assessed the relationship between levels of sE-cad in coronal sulcus swabs to membrane-bound E-cadherin in the overlying foreskin tissue in Ugandan men.
sE-cad levels immediately increased after in vitro epithelial physical disruption with the degree of elevation dependent on the extent of disruption, as did levels of IL-1β and IL-1α; this was followed by a delayed increase in IL-6 levels. In vivo results confirmed that sE-cad levels in cervicovaginal secretions were elevated 6 h after cytobrush sampling when compared to baseline. Furthermore, levels of sE-cad in the prepuce were inversely correlated with the amount of membrane-bound E-cadherin of overlying tissue.
Our results validate the use of sE-cad as a marker of epithelial disruption and demonstrate that the processes of physical disruption and inflammation in the genital tract are strongly intertwined.
摘要：
目的：生殖器上皮屏障是防御HIV的重要第一道防线，上皮破坏可能增强HIV易感性。评估生殖器上皮完整性需要活检，但是它们的收集在许多研究环境中并不实用。因此,验证的生殖器上皮屏障完整性的生物标志物将是有用的。这项研究的目的是评估可溶性E-cadherin（sE-cad）作为生殖器上皮破坏的标志物。
方法：使用宫颈和包皮上皮细胞的体外模型，我们评估了sE-cad的变化，IL-6，IL-1β，和机械破坏后的IL-1α水平。我们还通过宫颈内膜细胞刷采样评估了上皮破坏后宫颈阴道分泌物体内sE-cad水平的变化，并评估了冠状沟拭子中sE-cad水平与上覆包皮组织中膜结合的E-cadherin之间的关系。
结果：sEcad水平在体外上皮物理破坏后立即升高，其升高程度取决于破坏程度，IL-1β和IL-1α的水平，随后是IL-6水平的延迟增加。体内结果证实,与基线相比,在细胞刷取样后6小时,宫颈阴道分泌物中的sE-cad水平升高。此外，包皮中sE-cad的水平与上覆组织的膜结合E-cadherin的量呈负相关。
结论：我们的结果验证了sE-cad作为上皮破坏的标志物，并表明生殖道的物理破坏和炎症过程强烈交织在一起。本文受版权保护。保留所有权利。
方法：使用宫颈和包皮上皮细胞的体外模型，我们评估了sE-cad的变化，IL-6，IL-1β，和机械破坏后的IL-1α水平。我们还通过宫颈内膜细胞刷采样评估了上皮破坏后宫颈阴道分泌物体内sE-cad水平的变化，并评估了冠状沟拭子中sE-cad水平与上覆包皮组织中膜结合的E-cadherin之间的关系。
结果：sEcad水平在体外上皮物理破坏后立即升高，其升高程度取决于破坏程度，IL-1β和IL-1α的水平，随后是IL-6水平的延迟增加。体内结果证实,与基线相比,在细胞刷取样后6小时,宫颈阴道分泌物中的sE-cad水平升高。此外，包皮中sE-cad的水平与上覆组织的膜结合E-cadherin的量呈负相关。
结论：我们的结果验证了sE-cad作为上皮破坏的标志物，并表明生殖道的物理破坏和炎症过程强烈交织在一起。本文受版权保护。保留所有权利。
