MOLECULAR MECHANISMS AND CLINICAL APPLICATION OF ULTRAVIOLET A THERAPY

紫外线A疗法的分子机制及临床应用

• 批准号: 10670801
• 负责人: MORITA Akimichi
• 金额: $ 2.43万
• 依托单位: NAGOYA CITY UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670801/
• 关键词: ULTRAVIOLET RADIATION; PHOTOTHERAPY; SKIN DISEASE; SCLEROSIS; APOPTOSIS; FAS; COLLAGEN; METALLOPROTEINASE

The purpose of this study was to investigate the underlying mechanisms and the clinical application of UVA1 phototherapy for skin diseases, e.g., atopic dermatitis, cutaneous T cell lymphoma and systemic sclerosis. UVA1 can penetrate through the epidermis to the deep dermis. No apoptosis was induced in keratinocytes and fibroblasts with 30-50 J/cmィイD12ィエD1 of UVA1 (430-400), which easily mediated T cell apoptosis. UVA1 induced FASL surface expression in keratinocytes if they were treated with metalloprotease inhibitor. Soluble FASL (sFASL) was also detected in the supernatant of UVA1-irradiated keratinocytes. The supernatant mediated apoptosis of FAS-expressing T cells with the treatment of the supernatant, which was partially inhibited with FASL antibody. The result suggested that sFASL from UVA1-irradiated keratinocytes mediated apoptosis of the infiltrating T cells in the lesion through paracrine mechanism. In fibroblasts, UVA1 upregulated metalloprotease (MMP)1, 3 but not TIMP-1, 3. It suggested that UVA1 might be effective for fibrous diseases, e.g., scleroderma. Based on the in vitro results, UVA1 therapy was attempted for the treatment of cutaneous malignant T cells and systemic sclerosis. The therapeutic effectiveness was found in both diseases.

本研究的目的是探讨UVA1光疗治疗特应性皮炎、皮肤T细胞淋巴瘤和系统性硬化症等皮肤病的潜在机制和临床应用。 UVA1可以穿透表皮到达真皮深层。 UVA1（430-400）的30-50 J/cmィイD12ィエD1不会诱导角质形成细胞和成纤维细胞凋亡，容易介导T细胞凋亡。如果用金属蛋白酶抑制剂处理，UVA1 会诱导角质形成细胞中 FASL 表面表达。在 UVA1 照射的角质形成细胞的上清液中也检测到可溶性 FASL (sFASL)。上清液处理后介导表达FAS的T细胞凋亡，FASL抗体部分抑制了这种凋亡。结果表明，来自 UVA1 照射的角质形成细胞的 sFASL 通过旁分泌机制介导病变中浸润性 T 细胞的凋亡。在成纤维细胞中，UVA1 上调金属蛋白酶 (MMP)1, 3 但不上调 TIMP-1, 3。这表明 UVA1 可能对纤维性疾病（例如硬皮病）有效。根据体外结果，UVA1疗法被尝试用于治疗皮肤恶性T细胞和系统性硬化症。在这两种疾病中都发现了治疗效果。

项目成果

Akimichi Moria: "Ultraviolet A-1 (340-400 nm) Phototherapy for scleroderma in systemic sclerosis"Journal of American Academy of Dermatology. (印刷中).

Akimichi Moria：“紫外线 A-1（340-400 nm）光疗治疗系统性硬化症”美国皮肤病学会杂志（正在出版）。

Akimichi Morita: "Methods in enzymology, Singlet oxygen, UV-A & Ozone"Academic Press(L. Packer, H. Sies, eds)(印刷中).

Akimichi Morita：“酶学方法、单线态氧、UV-A 和臭氧”学术出版社（L. Packer、H. Sies 编辑）（正在印刷中）。

森田明理: "皮膚疾患に対する紫外線療法の今後"日本臨床皮膚科医学会雑誌. 63. 11-16 (2000)

Akari Morita：“皮肤病紫外线疗法的未来”日本临床皮肤病学会杂志 63. 11-16 (2000)。

Heidi Plettenberg: "Ultraviolet A-1(340-400 nm) phototherapy for cutaneous T cell lymphoma"Journal of America Academy of Dermatology. 41. 47-50 (1999)

Heidi Plettenberg：“紫外线 A-1（340-400 nm）光疗治疗皮肤 T 细胞淋巴瘤”美国皮肤病学会杂志。

Jean Krutmann: "Mechanisms of ultraviolet (UV) B and UVA phototherapy"Journal of Investigative Dermatology Symposium Proceedings. 4. 70-72 (1999)

Jean Krutmann：“紫外线 (UV) B 和 UVA 光疗的机制”皮肤病学研究杂志研讨会论文集。