ERa对CD4+T淋巴细胞在良性前列腺增生中的调控作用及机制研究

Benign prostatic hyperplasia (BPH) is one of the most common diseases in aging men. Etiology of BPH is still poorly understood. Lots of CD4+T lymphocytes had been found in BPH tissues. Estrogen can regulate innate immune response. ER express increases in human BPH tissues. Animal experiments show that ER but not ER is necessary for inducing BPH growth. But the relationship between ER and CD4+T lymphocytes and the mechanisms still unclear. Our early results showed that ①Estrogen could increase more CD4+T lymphocytes migration and more CXCL-12 released. ER knock down can block the migration. ②ER、CD4、CXCL-12 co-located in BPH tissues. ③ CD4+T lymphocytes can induce BPH cell proliferation. Hence, we hypothesis that⑴ER promoter can bind to CXCL-12 regulate CD4+T lymphocytes chemotaxis.(2) CD4+T lymphocytes release cytokine and active proliferation associated gene or signal pathway to increase BPH growth through BPH ER. Therefore we plan to intervene BPH ER then: 1. Investigate the mechanisms of chemotaxis of CD4+T lymphocytes to BPH. 2. Observe the proliferated effect CD4+T lymphocytes on BPH through ER.3. Discuss the mechanisms of proliferation.

BPH是老年男性常见病和多发病，病因不清。BPH组织中有大量CD4+T细胞浸润，雌激素通过ER调节内源性免疫反应，而ER在人BPH表达增强。动物实验发现ER（非ER）对于激素诱导的前列腺增殖是必须的，但作用机制不清。我们前期研究发现：①雌激素可使CD4+T细胞趋化增加，释放CXCL-12等细胞因子，ER敲除则趋化作用降低；②ER、CD4、CXCL-12在BPH组织存在共分布；③CD4+T细胞促进BPH细胞增殖。因此我们假设：⑴ER启动子存在CXCL-12结合位点，调控CD4+T细胞趋化；⑵T细胞释放细胞因子作用于BPH细胞ER，并通过激活增殖相关基因或信号通路促进BPH细胞增殖。为此本课题拟对BPH细胞ER进行干预：⒈探讨ER对CD4+T细胞趋化作用机制；⒉观察CD4+T细胞通过ER对BPH的增殖作用；⒊探讨增殖作用的机制。期望为BPH的预防和治疗提供新的方法和途径。