Roles of sex hormones in the pathogenesis of psoriasis vulgaris and their therapeutic efficacy

这个项目的目的是调查性激素对1的影响。角化细胞的增殖、DNA合成或凋亡。角化细胞中自分泌生长因子的产生促炎性：角化细胞中促炎性或抗炎性细胞因子、趋化因子或血管生成因子的产生角化细胞中炎性细胞因子或生长因子的细胞粘附分子或受体的表达角质形成细胞中细胞角蛋白的表达。我们的项目1:17β-雌二醇（E2）结合角化细胞表面的GPR30，诱导cAMP信号，增强抗凋亡蛋白Bcl-2的表达，从而抑制氧化应激诱导的细胞凋亡。我们项目4的研究结果：(1)E2通过诱导角化细胞cAMP信号抑制jak1,2 /Stat1信号通路，从而抑制1型T细胞吸引趋化因子IP-10的表达。(2)E2抑制角质形成细胞Sp1和AP-1的转录活性，从而抑制单核细胞/巨噬细胞趋化因子MCP-1的表达。(3)E2抑制角质形成细胞中NF-κ b的转录活性，从而抑制RANTES、1型T细胞和单核/巨噬细胞趋化因子的表达。这些结果表明，E2可能抑制银屑病皮损中异常增强的角质形成细胞凋亡，维持皮肤稳态，E2可能抑制1型T细胞或单核/巨噬细胞浸润银屑病皮损，从而减轻炎症。这些结果表明E2对银屑病的治疗效果。项目2、3、5正在进行中。

The aim of this project is to investigate the effects of sex hormones on1.proliferation, DNA synthesis, or apoptosis in keratinocytes2.autocrine growth factor production in keratinocytes3.the production of pro- or anti-inflammatory cytokines, chemokines, or angiogenic factors in keratinocytes4.the expression of cell-adhesion molecules or receptors for inflammatory cytokines or growth factors in keratinocytes5.the expression of cytokeratins in keratinocytes.Our results on project 1:17β-estradiol (E2) binds GPR30 on the surface of keratinocytes and induces cAMP signal which enhances the expression of anti-apoptotic protein, Bcl-2 and thus suppresses apoptosis induced by oxidative stress.Our results on project 4 :(1)E2 suppresses Jak1,2/Stat1 signaling pathway via inducing cAMP signal in keratinocytes and thus suppresses the expression of IP-10, type 1 T cell-attracting chemokine.(2)E2 suppresses transcriptional activities of Sp1 and AP-1 in keratinocytes and thus suppresses the expression of MCP-1, monocyte/macrophage-attracting chemokine.(3)E2 suppresses transcriptional activity of NF-κB in keratinocytes and thus suppresses the expression of RANTES, type 1 T cell- and monocyte/macrophage-attracting chemokine.These results suggest that E2 may suppress abnormally enhanced apoptosis of keratinocytes in psoriatic lesions and maintain skin homeostasis and that E2 may suppress the infiltration of type 1 T cells or monocyte/macrophages into psoriatic skin lesions and thus attenuate inflammation. These results indicate therapeutic efficacy of E2 for psoriasis. Projects 2,3,5 are now on-going.