STAT3与黑素瘤

信号转导与转录激活因子3(STAT3)既是一种胞质信号分子又是胞核转录因子,参与细胞的存活、增殖、转化及迁移等过程.它在肿瘤如黑素瘤的发病中起着非常重要的作用,通过调节基因表达促进黑素瘤细胞的生长而参与肿瘤细胞的存活与增殖;通过诱导基因的表达促进黑素瘤细胞转移和肿瘤血管生成,参与调节肿瘤免疫侵袭所致的肿瘤免疫耐受.通过向目的细胞内引人STAT3反义寡核苷酸、诱饵寡核苷酸或显性负相蛋白等阻断STAT3的功能,可抑制目的细胞的增殖,促进细胞的死亡.     

Stat3在进行期寻常型银屑病皮损表皮中的表达

目的观察信号转导和转录激活因子3(Stat3)在银屑病皮损中的表达情况。方法应用免疫组化法检测正常组织、进行期寻常型银屑病皮损及非皮损表皮中Stat3蛋白表达。结果正常表皮细胞中Stat3低水平表达于胞浆中;寻常型银屑病进行期皮损表皮中Stat3表达于多数细胞的胞浆和胞核中;非皮损处表皮中Stat3表达于部分细胞的胞浆和(或)胞核中。皮损处Stat3评分与PASI呈正相关。结论Stat3在进行期寻常型银屑病表皮中有异常表达。     

雷帕霉素对Colo-16细胞系Stat3表达的影响

目的研究雷帕霉素对皮肤鳞状细胞癌Colo-16细胞系Stat3表达的影响。方法用不同浓度的雷帕霉素处理Colo-16细胞,Hoechst33258荧光染色法观察凋亡细胞的形态学变化;Western-blotting法检测Colo-16细胞Stat3,P-Stat3蛋白表达水平。结果雷帕霉素能够诱导Colo-16细胞凋亡,荧光染色可见细胞核染色质凝聚、核裂解的形态学改变;在雷帕霉素作用后Colo-16细胞Stat3,P-Stat3表达显著下调。结论雷帕霉素能诱导Colo-16细胞凋亡,其作用机制可能与Stat3表达下调有关。     

角蛋白K14反义寡核苷酸对角质形成细胞增殖的影响

目的：研究角蛋白K14反义寡核苷酸(ASODN)对人角质形成细胞(KC)体外增殖活性的影响。方法：利用脂质体将人工合成的正义、反义及错配K14寡核苷酸基因片段导人体外培养的角质形成细胞，应用细胞生长抑制实验、透射电镜(TEM)和流式细胞仪(FCM)检测ASODN对角质形成细胞的增生、超微结构改变和细胞增殖周期的影响。结果：脂质体介导的K14反义寡核苷酸组KC增殖活性受到明显抑制；电镜下可见KC增殖活性受到抑制的改变，角蛋白合成明显减少；流式细胞仪检测见细胞周期发生明显改变，G1期细胞百分率上升，S期细胞百分率下降。而正义寡核苷酸组、错义寡核苷酸组及空白对照组均无此改变。结论：K14反义寡核苷酸可抑制KC体外增殖活性，应用反义寡核苷酸技术封闭K14基因，有望为银屑病的基因治疗提供新的思路。     

生存素反义寡核苷酸对人恶性黑素瘤A375细胞生物学行为的影响

目的研究生存素反义寡核苷酸(AS-ODN)经脂质体介导转染对A375细胞增殖、凋亡的影响。方法合成生存素硫代反义寡核苷酸(AS-ODN),脂质体携带转染人恶性黑素瘤A375细胞。采用台盼蓝计数、软琼脂克隆形成试验、电镜、流式细胞仪检测AS-ODN对A375细胞增殖及凋亡的影响。通过裸鼠致瘤实验观察AS-ODN对A375细胞动物体内增殖的抑制作用。结果生存素反义寡核苷酸能降低G2/M期细胞百分比,诱导细胞凋亡发生,明显抑制A375细胞的生长和克隆形成,裸鼠体内A375细胞恶性增殖潜力下降。结论脂质体介导生存素AS-ODN能有效抑制A375细胞增殖、诱导肿瘤细胞凋亡。     

转录激活因子3、葡萄糖转运蛋白-1、增殖细胞核抗原在尖锐湿疣组织中的表达

目的 探讨尖锐湿疣组织中转录激活因子（Stat） 3、葡萄糖转运蛋白-1（GluT-1）、增殖细胞核抗原（PCNA）的表达及意义。方法 采用免疫组化SP法检测40例尖锐湿疣组织中Stat 3、GluT-1和PCNA的表达。结果 尖锐湿疣组织中Stat 3、GluT-1和PCNA阳性表达率分别为85.0%（34/40）、87.5%（35/40）和85.0%（34/40），正常人对照组分别为35.0%（7/20）、30.0%（6/20）和55.0%（11/20）；尖锐湿疣组织中Stat 3、GluT-1和PCNA阳性表达强度多为++ ～ +++，正常人对照组多在- ～ ++。尖锐湿疣组和对照组中Stat 3、GluT-1和PCNA阳性表达率及表达强度差异均有统计学意义（P < 0.05）。尖锐湿疣组织中PCNA与Stat 3和GluT-1表达强度间存在正相关性（P < 0.05），Stat 3与GluT-1表达呈正相关（P < 0.05）。结论 尖锐湿疣组织中存在Stat 3、GluT-1和PCNA过表达，Stat 3和GluT-1的过表达可能与尖锐湿疣组织的过度增殖有关。     

反义寡核苷酸阻遏角蛋白14的表达

目的 研究脂质体介导角蛋白K14反义寡核苷酸(ASODN)阻遏人角质形成细胞K14基因和蛋白的表达及抑制体外增殖活性的效果.方法 人表皮角质形成细胞原代培养,3~10代用于实验,利用脂质体将人工合成的正义、反义及错配K14寡核苷酸基因片段导入角质形成细胞,应用流式细胞仪、逆转录聚合酶链反应(RT-PCR)和免疫组化(SABC)方法检测反义寡核苷酸对角质形成细胞的细胞周期、K14基因和蛋白表达的影响.结果 脂质体介导的K14反义寡核苷酸转染角质形成细胞后,能有效地抑制角质形成细胞中K14基因的表达;48h后可阻遏K14蛋白表达;流式细胞仪检测见反义寡核苷酸处理组细胞周期发生明显改变,G₁期细胞百分率上升,S期细胞百分率下降.而正义寡核苷酸1组、错义寡核苷酸组及空白对照组均无此变化.结论 应用反义技术封闭K14基因,可以阻遏角蛋白K14基因和蛋白的表达,并可以抑制体外培养的角质形成细胞的增殖.     

皮肤科学基础

20042639　角蛋白K14反义寡核苷酸对角质形成细胞增殖的影响/陈玉欣(四军大西京医院全军皮肤性病中心)…//临床皮肤科杂志.-2004,33(5).-263～265采用脂质体将人工合成的正义、反义及错配寡核苷酸基因片段导入体外培养的角质形成细胞,应用细胞生长抑制实验、透射电镜和流式细胞仪分别检测反义寡核苷酸对角质形成细胞的增殖、超微结构和细胞增殖周期的影响。结果显示,脂质体介导的K14反义寡核苷酸对角质形成细胞的增殖活性有明显抑制作用;电镜下见角质形成细胞中角蛋白合成明显减少;流式细胞仪检测见细胞周期发生明显改变,G1期细胞百分率上…     

Stat1和含SH2区域的SHP-1在尖锐湿疣中的表达

目的 探讨JAK/STAT通路中信号转导和转录激活因子Stat 1和含SH2区域的酪氨酸磷酸酶SHP-1在尖锐湿疣中的异常表达。方法 原位杂交技术诊断HPV6/11相关尖锐湿疣,SP免疫组化染色技术检测40例HPV6/11阳性尖锐湿疣患者皮损、20例正常人皮肤(包皮)中Stat 1和SHP-1的表达及分布。结果 尖锐湿疣皮损中Stat 1和SHP-1的表达均强于正常人上皮中的表达,两者比较差异均有统计学意义(前者W=382.5,P<0.01;后者W=369,P<0.01)。尖锐湿疣患者皮损中Stat 1和SHP-1阳性细胞主要分布于棘细胞层,Stat 1阳性反应定位于胞浆或胞核,SHP-1阳性反应主要定位于胞浆。尖锐湿疣患者中Stat 1和SHP-1的表达呈显著相关性(tau-b=1.0,P<0.01)。结论 HPV6/11阳性尖锐湿疣中Stat 1和SHP-1表达增强,提示HPV6/11感染时可能通过JAK/STAT通路,在角质形成细胞过度增殖中起作用。     

Galectins and cutaneous immunity

Galectins are highly expressed in epithelial cells and immune cells. In skin, they can be detected in keratinocytes, melanocytes, dendritic cells, macrophages, and T cells. Galectins are present outside and inside the cells and thus may exhibit different functions through extracellular and intracellular actions. Galectins can be involved in the pathogenesis of inflammatory skin diseases by affecting growth, apoptosis, maturation, activation, and motility of keratinocytes and immune cells. Expression of galectins may change depending on the cellular status, such as proliferation and activation. For example, galectin-3 expression is upregulated in T cells but downregulated in dendritic cells when these cells are activated. Furthermore, their expression may also change under pathological conditions. Understanding the function of each galectin in keratinocytes and different immune cell types may reveal how galectins contribute to the pathogenesis of immune-mediated skin diseases.     

Critical role of the interleukin-23/T-helper 17 cell axis in the pathogenesis of psoriasis

Psoriasis is an inflammatory disease with dynamic interactions between the immune system and the skin. Recent studies have demonstrated that the interleukin (IL)-23/T-helper (Th)17 cell axis plays an important role in the pathogenesis of psoriasis. Here, the biology and function of Th17 cells as well as the crucial role of IL-23 in the context of the Th17 cell-dependent chronic inflammation in psoriatic skins are reviewed. Recent study about the role of the IL-23/Th17 axis in the pathogenesis of psoriasis-like lesions in K5.Stat3C transgenic mice is also discussed. This model mouse for psoriasis not only verifies the therapeutic efficacies of biologics that specifically target the IL-23/Th17 axis, but also clarifies the pathogenesis of psoriasis.     

TWEAK/Fn14信号在皮肤病诊断与治疗中的作用

肿瘤坏死因子样细胞弱凋亡因子(TWEAK)属于肿瘤坏死因子配体超家族成员,通过激活其受体成纤维细胞生长诱导因子14(Fn14)而发挥多种生物学功能。TWEAK/Fn14信号的激活可以调控细胞增殖、分化过程,促进纤维增生反应、血管形成和炎症反应,参与红斑狼疮、银屑病、皮肤肿瘤等疾病的发病过程。TWEAK在某些皮肤病患者的血清及尿液中表达上调,有潜力成为早期诊断及活动度评估的生物学标志物。适度激活TWEAK/Fn14信号可促进皮肤创伤愈合,但过强或延长激活该信号则会导致各种病理性组织损害,故激活或阻断该信号的特定环节有望成为治疗皮肤病的新策略。本文综述了TWEAK/Fn14信号在皮肤病发病机制中的作用,探讨该信号在相关诊断与治疗中的潜在价值。     

Th17细胞在皮肤病的研究进展

Th17细胞不同于Th1、Th2细胞.它由记忆CD4+T细胞、初始T细胞等在IL-6和转化生长因子β、IL-1β或IL-23的作用下分化而来的.成熟的Th17细胞分泌IL-17、IL-22等多种细胞因子,在自身免疫疾病、宿主防御、炎症、肿瘤、移植物排斥等多种病理过程中起着重要的作用.概述Th17细胞的分化、相关细胞因子,以及在皮肤病发病机制中的作用.

Abstract：

Th17 cells are different from Th1 and Th2 cells. They are differentiated from memory CD4+T cells and naive T cells induced by interleukin (IL)-6, transforming growth factor (TGF) 3, IL-1β or IL-23.Mature Th17 cells can secrete many cytokines, such as IL-17, IL-22, etc, and play a crucial role in the pathological process of autoimmune diseases, host defense, inflammatory diseases, tumors and graft-versus-host diseases. This review presents the differentiation and related cytokines of Th17 cells as well as their roles in the pathogenesis of skin diseases.     

IL-21 in the pathogenesis and treatment of skin diseases

Interleukin-21 (IL-21) is a potent immunomodulatory cytokine, with pleiotropic effects on both innate and adaptive immune responses. These actions include positive effects, such as enhanced proliferation of lymphoid cells, increased cytotoxicity of CD8(+) T cells and natural killer cells, and differentiation of B cells into plasma cells. IL-21 is also produced by Th17 cells and is a critical regulator of Th17 development. IL-21 has potent antitumor activity, but is also associated with the development of autoimmune disease. Many of these activities are critically involved in the pathogenesis of several skin diseases such as psoriasis, atopic dermatitis, lupus erythematosus, and melanoma. Here we review recent advancements on the understanding of the role of IL-21 in skin diseases and how this knowledge can be translated into innovative therapeutic approaches.