Analysis of prion protein expression on human cutaneous dendritic cells

人皮肤树突状细胞朊病毒蛋白表达分析

• 批准号: 14570817
• 负责人: NAKAMURA Koichiro
• 金额: $ 1.34万
• 依托单位: Fukushima Medical University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570817/
• 关键词: Langerhans cells; IL-1; TNF-α; Prion; 樹状細胞

Prions are infectious particles which forms abnormal isoforms of prion protein (acrapie-associated PrP) of the ubiquitous prion-related protein (PrPc). Various tissues such as spleen, lung and uterus have been reported to express PrPc. We investigated whether Langerhans cells, epidermal dendritic cells that stimulate T cells in the afferent lymph nodes expressed PrPc. We succeeded to purify LC from the skin over 95% purity and identified that LC expressed strong intensity for PrPc on cell surface membrane. In vitro expreriment showed that PrPc expression on LC was enhanced by additional stimulation of IL-1 and TNF-α : Furthermore, we next purified dendritic epidermal T cells (DETC) and found that these T cells also expressed PrPc. The experiment using PrP knockout mice showed that the PrPc expression on LC and DETC was totally diminished and that no cytokines including IL-1 and TNF-α did not modulate PrPc expression on these cells. These data revealed the dynamic change of PrPc expression of epidermal densritic cells. Our data will have some role in the understanding of the pathogenesis of PrP-related diseases and to help the future thera eutic a roaches to treat PrP-relat diseases.

朊病毒是普遍存在的朊病毒相关蛋白（PrPc）的朊病毒蛋白（acrapie-associated PrP）的异常同种型的感染性颗粒。已报道多种组织如脾、肺和子宫表达PrPc。我们研究了朗格汉斯细胞，表皮树突状细胞，刺激T细胞在传入淋巴结表达PrPc。我们成功地从皮肤中纯化了纯度超过95%的LC，并鉴定了LC在细胞表面膜上表达强强度的PrPc。体外实验表明，IL-1和TNF-α刺激可增强LC表面PrPc的表达。进一步纯化的树突状表皮T细胞（DETC）也表达PrPc。用PrP基因敲除小鼠的实验表明，LC和DETC上的PrPc表达完全减少，并且没有细胞因子包括IL-1和TNF-α不调节这些细胞上的PrPc表达。这些数据揭示了表皮致密细胞PrPc表达的动态变化。本研究的结果对深入了解PrP相关疾病的发病机制和指导今后的蟑螂治疗PrP相关疾病具有一定的参考价值。

项目成果

XZheng, Nakamura K, et al.: "TGF-β_1-mediated regulation of thymus and activation regulated chemokine synthesis and seaetion by HaCaT cells co-stimulated with TNFα and 1FN-γ"Journal of Dermatological Science. 30(2). 154-160 (2002)

XZheng、Nakamura K 等人：“TGF-β_1 介导的胸腺调节以及与 TNFα 和 1FN-γ 共同刺激的 HaCaT 细胞的活化调节趋化因子合成和分泌”《皮肤病学杂志》30(2)。 160 (2002)

Kakinuma T, Nakamura K, et al.: "IL-4, but not IL-13, modulate TARC/CCL17 and IP-10/CXCL10 relesed by TNF-alpha and IFN-gamma in HacaT cell line"Cytokine. 20(1). 1-6 (2002)

Kakinuma T、Nakamura K 等人：“IL-4（而非 IL-13）调节 HacaT 细胞系中 TNF-α 和 IFN-γ 释放的 TARC/CCL17 和 IP-10/CXCL10”细胞因子。

Kagami S, Kakinuma T, Saeki H, Nakamura K, et al.: "Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis : serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis."

Kagami S、Kakinuma T、Saeki H、Nakamura K 等人：“特应性皮炎患者中 eotaxin-3/CCL26 血清水平显着升高，但 eotaxin-2/CCL24 水平不显着升高：血清 eotaxin-3/CCL26

Kakinuma T, Sugaya M, Nakamura K, et al.: "Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides : serum TARC levels reflect the disease activity of mycosis fungoides"J Am Acad Dermatol. 48(1). 23-30 (2003)

Kakinuma T、Sugaya M、Nakamura K 等人：“蕈样肉芽肿中的胸腺和活化调节趋化因子 (TARC/CCL17)：血清 TARC 水平反映了蕈样肉芽肿的疾病活动性”J Am Acad Dermatol。

Zheng X, Nakamura K, Tojo M, Akiba H, Y, et al.: "Ultraviolet A irradiation inhibits thymus and activation-regulated chemokine (TARC/CCL17) production by a human keratinocyte HaCaT cell line"Eur J Dermatol. 13(4). 348-353 (2003)

Cheng X、Nakamura K、Tojo M、Akiba H、Y 等人：“紫外线 A 照射抑制人角质形成细胞 HaCaT 细胞系的胸腺和活化调节趋化因子 (TARC/CCL17) 的产生”Eur J Dermatol。