A study for atopic dermatitis controlledby Caspase-1 and IL-18

Caspase-1和IL-18控制特应性皮炎的研究

• 批准号: 13470171
• 负责人: MIZUTANI Hitoshi
• 金额: $ 9.02万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470171/
• 关键词: IL-18; IL-1; hiatamine; caspase; Atopic dermatitis; Innate immunity; Innate atopy; psoriasis; IL-8; in nate atopy

We have established two transgenic mice (skin specifically caspase-1 and IL-18 overexpressed mice), and these mice developed persistent dermatitis similar to the human atopic dermatitis (AD). The skin and systemic immune systems of these mice were allergic type shifted to Th2 conditions, secreting IL-18, IL-4, IL-5 and IL-10. Dermal mastocytosis and hyper histaminemia resulted in intensive scratching behaviour as a characteristic model for atopic dermatitis, and significant elevation of serum IgE levels. IgE-/-Caspase-1Tg persisted AD type skin lesions, but extermination of IL-18 completely suppressed development of the skin lesions, which strongly supported IL-18 dependency of this dermatitis. Because these lesions were independent from the exogenous allergens, we proposed a new concept as innate type atopy in contrast to the allergen dependent IgE mediated atopy. We successfully treated the skin manifestations of the caspase-1Tg using BCG vaccination with suppressed IL-18 production. We also developed Stat6-/-caspase-1Tg, which developed skin lesions mimic pustular psoriasis without Th2 shift. These studies revealed importance of the percutaneous IL-18secretion in both of Th2 type AD and Th1 type psoriasis.

我们已经建立了两只转基因小鼠(皮肤特异性表达caspase-1和IL-18的小鼠)，这些小鼠发生了类似于人类特应性皮炎(AD)的持续性皮炎。这些小鼠的皮肤和全身免疫系统均为过敏型，向Th2状态转变，分泌IL-18、IL-4、IL-5和IL-10。皮肤肥大细胞增多症和高组胺血症导致强烈的抓挠行为，作为特应性皮炎的特征模型，并显著提高血清IgE水平。Ige-/-Caspase-1TG持续存在AD皮损，但IL-18的根除完全抑制了皮损的发展，这有力地支持了这种皮炎对IL-18的依赖。由于这些病变不依赖于外源性过敏原，我们提出了先天类型特应性的新概念，与过敏原依赖的IgE介导的特应性不同。我们成功地用卡介苗接种治疗了caspase-1TG的皮肤表现，并抑制了IL-18的产生。我们还开发了Stat6-/-caspase-1TG，它的皮肤病变类似于脓疱性银屑病，没有Th2移位。这些研究揭示了经皮IL-18分泌在Th2型AD和Th1型银屑病中的重要性。

项目成果

Mizutani, H., Nishiguchi, K., Murakami, T.: "Model mouse for atopic dermatitis."Nihonishikaizasshi. 129. 1409-1413 (2003)

Mizutani, H.、Nishiguchi, K.、Murakami, T.：“特应性皮炎模型小鼠。”Nihonishikaizasshi。

山中恵一ほか: "IL-18とアトピー性皮膚炎モデルマウス"アレルギー科. 13. 500-504 (2002)

Keiichi Yamanaka 等人：“IL-18 和特应性皮炎模型小鼠”过敏系 13. 500-504 (2002)。

水谷仁, 高橋眞智子, 清水正之ほか: "アトピー性皮膚炎患者に対する合成疑似セラミド含有クリームの有用性の検討"西日本皮膚科. 63. 457-461 (2001)

Hitoshi Mizutani、Machiko Takahashi、Masayuki Shimizu 等人：“合成假神经酰胺乳膏对特应性皮炎患者的有效性评估”West Japan Dermatology 63. 457-461 (2001)。

Nakano H, Mizutani H, et al.: "Persistent secretion of IL-18 in the skin contributes to IgE response in mice"Int Immunol. 15. 611-621 (2003)

Nakano H、Mizutani H 等人：“皮肤中 IL-18 的持续分泌有助于小鼠的 IgE 反应”IntImmunol。

Murakami, T., Yamanaka, k., Yoshikawa, Y., Mizutani, H.: "Effects of topical IPD for atopic model mouse"Nishinihon hifuka (Japanese). 64. 490-491 (2002)

Murakami, T.、Yamanaka, k.、Yoshikawa, Y.、Mizutani, H.：“局部 IPD 对特应性模型小鼠的影响”Nishinihon hifuka（日语）。