HUMAN DEFENSIN 5 IN FEMALE GENITAL TRACT IMMUNE DEFENSE

需要新的策略来预防和治疗性传播疾病 感染. α和β防御素是一个小家族， 在哺乳动物嗜中性粒细胞中表达的富含半胱氨酸的肽， 上皮细胞，并且其表现出抗微生物活性， 广泛的细菌、真菌和包膜病毒。 人防御素-5 （HD-5）是α-防御素家族的新成员，迄今为止， 在小肠的潘氏细胞中被发现。 的 研究人员最近在上皮细胞中发现了HD-5同源物， 人类女性生殖道的一部分 他们已经证明HD-5是 在肠道的不同区域差异表达， 表达被炎性过程改变，并且被炎症的阶段改变。 月经周期 本提案中概述的实验将测试 以下假设：（a）HD-5在女性生殖道中的表达 上皮细胞被性传播病原体上调， 促炎细胞因子和雌性生殖激素（B）HD-5是 分泌到生殖道腔，（c）HD-5具有有效的 对常见的性传播生物的杀微生物特性， 和（d）HD-5是白细胞的化学引诱物。 这项研究将 有助于阐明防御素在生殖道粘膜表面的作用， 并可能促进新的预防和治疗药物的开发， 针对性传播病原体的药剂，其基于这些 内源性抗生素肽

Novel strategies are needed to prevent and treat sexually transmitted infections. The alpha and beta defensins are a family of small, cysteine-rich peptides that are expressed in mammalian neutrophils and epithelial cells, and which exhibit antimicrobial activity against a wide range of bacteria, fungi and enveloped viruses. Human defensin-5 (HD-5) is a novel member of the a-defensin family which to date has only been found in the Paneth cells of the small intestine. The investigators recently detected a HD-5 homologue in the epithelial cells of the human female genital tract. They have demonstrated that HD-5 is differentially expressed in different regions of the tract and that expression is altered by inflammatory processes and by the stage of the menstrual cycle. The experiments outlined in this proposal will test the following hypotheses: (a) expression of HD-5 in female genital tract epithelia is upregulated by sexually transmitted pathogens, proinflammatory cytokines, and female reproductive hormones (b) HD-5 is secreted into the genital tract lumen, (c) HD-5 has effective microbicidal properties against common sexually transmitted organisms, and (d) HD-5 is a chemoattractant for leukocytes. This research will help elucidate the role of defensins at genital tract mucosal surfaces, and may facilitate the development of novel prophylactic and therapeutic agents against sexually transmitted pathogens which are based on these endogenous antibiotic peptides.