Effects of Male Circumcision on Human Penile Epithelia

描述(由申请人提供)：男性包皮环切术已被证明在临床上有效地降低了非洲男性的艾滋病毒感染率。减少HIV传播的科学基础仍不清楚，我们实验室的工作表明，其机制比早期理论上的机制复杂得多(关于角蛋白厚度和潜在HIV靶细胞的数量)。我们发现，阴茎上皮更动态的特性，如通透性和炎症反应，可能起到更重要的作用。这项建议致力于进一步探索男性包皮环切术后阴茎上皮细胞的变化，这些变化与皮肤的屏障功能有关，并将它们与之前接受包皮环切术和未环切术的人群进行比较。辅助研究将集中在包皮中基线结合蛋白的表达和可能影响男性艾滋病毒易感性的临床因素的研究。通过这些研究，我们希望更好地了解艾滋病毒是如何在男性生殖道性传播的，男性包皮环切术如何预防这种情况，以及如何制定未来有效的艾滋病毒预防策略。 公共卫生相关性：很明显，男性包皮环切术降低了女性对男性感染艾滋病毒的比率。这里提出的研究试图界定保护机制。了解这一机制应该会导致新的战略，以减少艾滋病毒从女性到男性的性传播。

DESCRIPTION (provided by applicant): Male circumcision has been shown to be clinically effective in reducing HIV acquisition rates in African men. The scientific rationale for the reduction in HIV transmission remains unknown, and work in our laboratory has shown that the mechanism is much more complex than those theorized early on (regarding keratin thicknesses and number of potential HIV target cells). We have found that more dynamic properties of the penile epithelia, such as permeability and inflammatory responses, may play more important roles. This proposal endeavors to further explore changes in penile epithelia after male circumcision, which relate to the skin's barrier function, and to compare them to previously circumcised and uncircumcised cohorts. Adjunct studies will focus on studies of baseline junctional protein expression in the foreskin and clinical factors that may affect HIV susceptibiliy in men. With these studies, we hope to gain a better understanding of how HIV is sexually transmitted in the male genital tract, how male circumcision works to prevent this, and how to develop effective future strategies in HIV prevention. PUBLIC HEALTH RELEVANCE: It is clear that male circumcision decreases the rate of female-to-male HIV acquisition. The studies proposed here seek to define the mechanism of protection. Understanding this mechanism should lead to new strategies which can decrease female-to-male HIV sexual transmission.