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Research on the mechanism of bullous diseases-Immunological and biological studies-

大疱性疾病发病机制研究-免疫学和生物学研究-

基本信息

批准号：
07459020
负责人：
SUZUKI Masayuki
金额：
$ 3.78万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07459020/
关键词：
Bullous Pemphigoid IgG subclass intracellular Ca^<2+>Proteoglycan Plectin adhesion molecule mucous membrane bullous diseases auto immune complements signal transduction adhesion molecules gene cell to stroma interaction conple

项目摘要

We have been studied the function and structure of cutaneous basement membrane zone (BMZ), and the pathogenesis of autoimmune bullous diseases. We have been contributed to the solution of the pathogenesis of the disease on BMZ of the other organs (ex.mucous membrane etc.). We get the fruits as follows. (1) The study of signal transduction. It was reported the possibility of transmembrane signalling exerted by pemphigus IgG binding keratinocytes. We reported a transient increase of intracellular Ca^<2+> concentration ( [Ca^<2+>]i) induced by IgG from the patients with bullous pemphigoid (BP), and the inhibition of this increase by the addition of phospholipase C inhibitor (Autoimmunity, 1996). These results suggested the possibility of transmembrane signaling exerted by BP IgG binding keratinocyte. (2) The study of the role of IgG subclass in the pathogenesis of BP : We reported that BP IgG_1 mainly in duce a transient in crease of [Ca^<2+>]i, and BP IgG_2 and IgG_4 inhibit an increase … More of [Ca^<2+>]i induced by BP IgG_1 (Autoimmunity, 1996 and submitted). In pemphigus, it was reported that a switching of IgG subclass was observed, and the possibility that IgG_4 serves as blocking antibody. On the other hand, we reported that there was a low possibility of IgG subclass switching in BP (submitted). In BP,the main IgG subclass were IgG_1 and IgG_4. The anti-BMZ autibody IgG titer was correlated with anti-BMZ IgG_1 and IgG_4. (3) The study of structure of BMZ.We examined the origins of BMZ chondroitin sulfate proteoglycan of BMZ of dermal-epidermal junction and hair follicle epithelium are of epidermal origin (J.J.D., 1996). Then we contributed to the solution of the pathogenesis of epidermolysis bullous simplex associated with late-onset muscular dystrophy (Human Molecular Genetics, 1996). (4) The study of cell adhesion molecule in oral mucous membrane. We examined the expression and localization of adhesion molecules in human normal oral mucous, tongue and gingiva, immunohistochemically. Integrin alpha5 was detected only in mucous membrane but not in tongues and gingiva (Oral oncology, 1995). The distribution of integrin alpha2, alpha3, alpha6, beta1, beta3 and beta4, and E-cadherin, P-cadherin, desmoglain and ICAM-1 was no significant change among mucous membrane, tongue and gingiva. Less

本文对皮肤基底膜带（BMZ）的结构和功能以及自身免疫性大疱病的发病机制进行了研究。为解决本病在其他器官（如粘膜等）BMZ上的发病机制做出了贡献。我们得到的水果如下。(1)信号传导学对信号传导的研究据报道，天疱疮IgG结合角质形成细胞产生跨膜信号的可能性。我们报道了大疱性类天疱疮（BP）患者IgG引起的细胞内Ca^<2 +>浓度（[Ca^<2+]i）的短暂升高，而加入磷脂酶C抑制剂可抑制这种升高（Autoimmunity，1996）。这些结果提示BPIgG结合角质形成细胞可能产生跨膜信号。(2)IgG亚类在BP发病中作用的研究：BPIgG_1主要引起[Ca^<2+>]i的一过性升高，BPIgG_2和IgG_4抑制[Ca^<2 +>] i的升高 ...更多信息 BPIgG_1诱导的[Ca^<2+>]i（Autoimmunity，1996 and submitted）。据报道，在天疱疮中观察到了IgG亚类的转换，并且IgG_4可能充当封闭抗体。另一方面，我们报告了BP中IgG亚类转换的可能性较低（已提交）。BP患者IgG亚类以IgG_1和IgG_4为主。抗BMZ抗体IgG滴度与抗BMZ抗体IgG_1、IgG_4呈显著正相关。(3)BMZ结构的研究。我们检查了BMZ硫酸软骨素蛋白聚糖的来源，真皮-表皮连接部和毛囊上皮的BMZ的蛋白聚糖是表皮来源的（J.J.D.，1996年）的报告。然后，我们致力于解决与迟发性肌营养不良症相关的表皮大疱性单纯症的发病机制（人类分子遗传学，1996年）。(4)口腔粘膜细胞粘附分子的研究。我们检测了粘附分子的表达和定位在人类正常口腔粘膜，舌和牙龈，免疫化学。整联蛋白α 5仅在粘膜中检测到，而在舌和牙龈中未检测到（Oral oncology，1995）。整合素α 2、α 3、α 6、β 1、β 3和β 4以及E-cadherin、P-cadherin、desmoglain和ICAM-1在粘膜、舌和牙龈中的分布无明显变化。少