Development of anti-skin ulcer drug based on the new concept-application of the effect of TNF-alpha on regeneration of peripheral nerve.

基于TNF-α对周围神经再生作用的应用新理念开发抗皮肤溃疡药物。

• 批准号: 06557050
• 负责人: TAKIGAWA Masahiro
• 金额: $ 9.15万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06557050/
• 关键词: skin ulser; wound healing; TNF-alpha; nerve regeneration; 腫瘍壊死因子; 神経成長因子; 線維芽細胞; サイトカイン; シグナル伝達; MAPキナーゼ

The effect of topical TNF-alpha on cutaneous wound repair with special reference to regeneration of periopheral nerve was investigated in C57BL/KsJ (db/db JcL) that spontaneously develop type II Diabetes Melitus. TNF-alpha at doses of 10 and 100ng, 1 and 10 mug and PBS as control were applied to full thickness skin wound (ca 1cm^2) in dorsal skin. The area of wound was measured and skin specimens were obtained periodically.1) Regression rate of wound was significantly higher on day 11 in mice treated with 100ngTNF-alpha than control. However, wound worsened in mice that received 1 and 10mugTNF-alpha as compaired with control.2) Wound was more mature on 14 day in mice treated with 100ngTNF-alpha than control, as exemplified by a decrease in number of neutrophils and eosinophiles in the dermal cellular infiltrate.3) In the TNF-alpha-treated group regeneration of preripheral nerve was apparent on day 14 compared with control, because nerve fibers were occasionally stained with an antineurofilament protein antibody.These results suggest that TNF-alpha at appropriate concentrations is expected to accelerate cutaneous wound healing, especially in terms of nerve regeneration.

在C57BL/KSJ（DB/DB JCL）中研究了局部TNF-Alpha对皮肤伤口修复的影响，该影响自发地发展了II型糖尿病融合体。 tnf-alpha的剂量为10和100ng，1和10杯和PBS作为对照的tnf-alpha在背皮肤中施加到全厚性皮肤伤口（Ca 1cm^2）上。测量伤口面积并定期获得皮肤标本。1）在用100NGTNF-ALPHA处理的小鼠中，第11天的伤口回落率明显高于对照。然而，与对照相比，接收1和10mugtnf-alpha的小鼠中的伤口更加恶化。2）受伤的14天，在用100ngtnf-α治疗的小鼠中，伤口更成熟，而对照组的伤口更为成熟，而对照组的伤口比对照组的伤口更为成熟，这是由中性粒细胞和嗜酸性粒细胞数量减少的体现。与对照组相比，在第14天相比，前神经明显是显而易见的，因为偶尔用抗金属丝蛋白抗体染色神经纤维。这些结果表明，预计以适当浓度的TNF-α可以加速皮肤皮肤伤口愈合，尤其是在神经再生方面。

项目成果

Hisashi Wakita: "Staphylococcal enterotoxin B upregulates expression of ICAM-1 molecules on IFN-n-treated keratinocytes and Keratinocyte cell lines" Journal of Investigative Dermatology. 105. 536-542 (1995)

Hisashi Wakita：“葡萄球菌肠毒素 B 上调 IFN-n 处理的角质形成细胞和角质形成细胞细胞系上 ICAM-1 分子的表达”《皮肤病学研究杂志》。

Keiji Iwatsuki: "Diversity of immunobiological functions of T-ceu lines established from patients with adult T-ceu leukemia." British Journal of Dermatology. 133. 861-867 (1995)

Keiji Iwatsuki：“从成人 T-ceu 白血病患者建立的 T-ceu 系的免疫生物学功能的多样性。”

Hattori A.: "Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon-gamma in stimulating the production of nerve growth factor in fibroblasts." FEBS Letters. 340. 177-180 (1994)

Hattori A.：“肿瘤坏死因子与白细胞介素 1 和干扰素-γ 显着协同刺激成纤维细胞中神经生长因子的产生。”

Iwatsuki K.: "Diversity of immunobiological functions of T-cell lines established from patients with adult T-cell Leukaemia." British Journal of Dermatology. 133. 861-867 (1995)

Iwatsuki K.：“从成人 T 细胞白血病患者建立的 T 细胞系的免疫生物学功能的多样性。”

Hisashi Wakita: "Staphylococcal enterotoxin B upregulates expression of ICAM-1 molecules on IFN-γ-treated keratinocytes and keratinocyte cell lines" Journal of Investigative Dermatology. 105. 536-542 (1995)

Hisashi Wakita：“葡萄球菌肠毒素 B 上调 IFN-γ 处理的角质形成细胞和角质形成细胞系上 ICAM-1 分子的表达”《皮肤病学研究杂志》105. 536-542 (1995)。