Transmembrane Signalling System in Psoriasis

银屑病跨膜信号系统

• 批准号: 03670519
• 负责人: IIZUKA Hajime
• 金额: $ 1.28万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670519/
• 关键词: psoriasis; protein kinase C; involucrin; retinoid; keratinization; cyclic AMP; TPA; プロテイン キナーゼ; 表皮; アデニル酸ミクラ-ゼ; βアドレナリン受容体; グルココルチコイド; プロテインキナ-ゼC; 脱感作; G蛋白質

1) Psoriatic involved epidermis was characterized by defective beta-adrenergic adenylate cyclase response. This was observed by the treatment of keratinocytes with protein kinase C activators as well as by the treatment of cells with the beta-adrenergic agonists.2) Glucocorticoids augment the beta-adrenergic adenylate cyclase response of keratinocytes through the induction of the beta2-adrenergic receptor.3) Protein kinase C activators induced the expression of involucrin, that is one of the major constituent of keratinocyte cornified envelope. The induction of involucrin by the protein kinase C activators was jun/fos-dependent process and was inhibited by glucocorticoids.4) Retinoid, Ro 10-1670, augmented the beta-adrenergic adenylate cyclase response in pig skin organ culture system. However, the retinoid decreased the beta-adrenergic adenylate cyclase response in FRSK culture system. In the latter system the decreased beta-adrenergic response was accompanied by the increased thymidine incorporation of FRSK cells.5) Superoxide dismutase activity was markedly decreased in the psoriatic involved epidermis. This was due to the decreased Cu, Zn-SOD activity. Immunohistochemical staining showed that the decreased Cu, Zn-SOD staining pattern was observed in the basal cell layr corresponding to the dermal papillae.

1)银屑病累及的表皮以β-肾上腺素能腺苷酸环化酶反应缺陷为特征。通过用蛋白激酶C激活剂处理角质形成细胞以及用β-肾上腺素能激动剂处理细胞观察到这一点。2）糖皮质激素通过诱导β 2-肾上腺素能受体来增强角质形成细胞的β-肾上腺素能腺苷酸环化酶反应。3）蛋白激酶C激活剂诱导外皮蛋白的表达，外皮蛋白是角质形成细胞外皮膜的主要成分之一。蛋白激酶C激活剂对外皮蛋白的诱导是jun/fos依赖性的，糖皮质激素可抑制外皮蛋白的诱导。4）维甲酸Ro 10-1670可增强猪皮肤器官培养系统中β-肾上腺素能腺苷酸环化酶的反应。然而，维甲酸降低β-肾上腺素能腺苷酸环化酶的反应在FRSK培养系统。在后者系统中，β-肾上腺素能反应的降低伴随着FRSK细胞胸苷掺入的增加。5）银屑病累及表皮的超氧化物歧化酶活性显著降低。这是由于Cu，Zn-SOD活性下降所致。免疫组织化学染色显示，在与真皮乳头相对应的基底细胞层，Cu，Zn-SOD的染色呈减弱型。

项目成果

飯塚一: "表皮細胞の増殖制御:カルモジュリンとその展開" 皮膚病診療. 15. 1034-1038 (1993)

Hajime Iizuka：“表皮细胞增殖的控制：钙调蛋白及其发育”《皮肤病理学》15. 1034-1038 (1993)。

Iizuka, H., Asaga, H., Koike, K., Iizuka, S.: "Decreased Cu, Zn-superoxide dismutase activity in psoriatic hyperproliferative epidermis." Eur J Dermatol. 3. 56-58 (1993)

Iizuka, H.、Asaga, H.、Koike, K.、Iizuka, S.：“银屑病过度增殖性表皮中铜、锌超氧化物歧化酶活性降低。”

H.Takahashi,H.Iizuka: "Neither cyclosporin A nor FK506 affects adenylate cyclase responses of FRSK cells at concentrations that inhibit thymidine incorporation." Journal of Dermatological Science. 6. 235-239 (1993)

H.Takahashi、H.Iizuka：“在抑制胸苷掺入的浓度下，环孢素 A 和 FK506 都不影响 FRSK 细胞的腺苷酸环化酶反应。”

H.Takahashi: "Analysis of the 5′-upstream promoter region of human involucrin gene" J Invest Dermatol. 100. 10-15 (1993)

H. Takahashi：“人外皮蛋白基因 5-上游启动子区域的分析”J Invest Dermatol. 100. 10-15 (1993)。

H.Takahashi,H.Iizuka: "Retinoid-induced beta-adrenergic inhibitory effect associated with increased thymidine incorporation of FRSK cells" Journal of Dermatological Science. 5. 122-129 (1993)

H.Takahashi、H.Iizuka：“类视黄醇诱导的 β-肾上腺素能抑制作用与 FRSK 细胞胸苷掺入增加相关”《皮肤病学杂志》。