Signal Transduction Induced by Desmosomal Cadherin Antigen-Antibody Reaction in Bullous Formation in Pemphigus

天疱疮大疱形成过程中桥粒钙粘蛋白抗原抗体反应诱导的信号转导

• 批准号: 07670938
• 负责人: SEISHIMA Mariko
• 金额: $ 1.54万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670938/
• 关键词: Pemphigus; Acantholysis; Desmosome; Intracellular Calcium; Phospholipase C; Plasminogen Activator; Signal Transduction; Protein Kinase C; 水疱症; 表皮細胞; Cキナーゼ; カルシウム

Pemphigus vulgaris (PV) is an autoimmune skin disease characterized by the autoantibodies against desmoglein 3. Although the exact mechanism for cutaneus blistering induced by PV-IgG binding to keratinocytes has not yet elucidated, pemphigus IgG-induced acantholysis may be caused by proteinases from keratinocytes such as plasminogen activator. We have studied the effects of PV-IgG on the intracellular signal transduction events, and demonstrated that PV-IgG-binding to DJM-1 cells (a squamous cell carcinoma line) induces a transient increase in phospholipase C activation, and an increased inositol 1,4,5-trisphophate production, with a concomitant increase in intracellular calcium concentration. These events are directly associated with secretion of plasminogen activator into the culture medium, and subsequent cell-cell detachment.In addition, the protein kinase C (PKC) activity in the particulate/cytoskeleton fraction was increased following PV-IgG exposure, peaking at 1 min, and being sustained for at leaset 30 min. These findings suggest that an activation profile of PKC may be involvedin mediationg the intracellular signaling events induced by PV-IgG binding to desmoglein 3 in cultured human keratinocytes.

寻常天疱疮（PV）是一种自身免疫性皮肤病，其特征在于针对桥粒芯糖蛋白3的自身抗体。虽然PV-IgG与角质形成细胞结合诱导皮肤起泡的确切机制尚未阐明，但天疱疮IgG诱导的棘层松解可能是由角质形成细胞的蛋白酶如纤溶酶原激活剂引起的。我们已经研究了PV-IgG对细胞内信号转导事件的影响，并证明PV-IgG与DJM-1细胞（鳞状细胞癌细胞系）结合诱导磷脂酶C活化的瞬时增加，以及增加的肌醇1，4，5-三磷酸生产，伴随着细胞内钙浓度的增加。这些事件与纤溶酶原激活剂分泌到培养基中以及随后的细胞-细胞分离直接相关。此外，在PV-IgG暴露后，颗粒/细胞骨架部分中的蛋白激酶C（PKC）活性增加，在1分钟时达到峰值，这些结果表明，PKC的激活模式可能参与介导细胞内信号转导在培养的人角质形成细胞中PV-IgG与桥粒芯糖蛋白3结合诱导的事件。

项目成果

Yasuo Kitajima: "A hemidesmosomal transmembrane collagenous molecule, the 180-kDa bullous pemphigoid antigen (BPA II), is phosphorylated with 12-0-tetradecanoylphorbol-13-acetate in a human squamous cell carcinoma cell line (DJM-1)" Epith Cell Biol. 4. 70

Yasuo Kitajima：“半桥粒跨膜胶原分子，即 180 kDa 大疱性类天疱疮抗原 (BPA II)，在人鳞状细胞癌细胞系 (DJM-1) 中被 12-0-十四烷酰佛波醇-13-乙酸酯磷酸化” Epith Cell

Kazuko Osada: "Pemphigus IgG activates and translocates protein kinase C from the cytosol to the particulate/cytoskeleton fractions in human keratinocytes" The Journal of Investigative Dermatology. (印刷中). (1997)

Kazuko Osada：“天疱疮 IgG 激活蛋白激酶 C，并将其从细胞质转移到人类角质形成细胞的颗粒/细胞骨架部分”《皮肤病学研究杂志》（1997 年出版）。

Mari Nojiri: "Immunofluorescence and immunoblot studies of herpetiform pemphigus" European Journal of Dermatology. 6. 406-408 (1996)

Mari Nojiri：“疱疹样天疱疮的免疫荧光和免疫印迹研究”欧洲皮肤病学杂志。

Kazuko Osada: "Pemphigus IgG activates and translocates protein kinase C from the cytosol to the particulate/cytoskeleton fractions in human keratinocytes" J Invest Dermatol. (in press). (1997)

Kazuko Osada：“天疱疮 IgG 激活蛋白激酶 C，并将其从细胞质转移到人角质形成细胞中的颗粒/细胞骨架部分”J Invest Dermatol。

Kazuko. Osada: "Pemphigus IgG activates and translocates protein kinase C from the cytosol to the particulate/cytoskeleton fractions in human keratinocytes" Journal of Investigative Dermatology. (1997)

和子。