Study for molecular and gene therapy of rheumatoid arthritis by targeting IL-6 signal transduction.

靶向IL-6信号转导的类风湿关节炎分子和基因治疗研究。

• 批准号: 10470126
• 负责人: NISHIMOTO Norihiro
• 金额: $ 1.47万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-10470126/
• 关键词: Rheumatoid Arthritis; Cytokine; Interleukin 6 (IL-6); TNFα; Humanized Antibody; IL-6 receptor; SSI-1; Negative feedback; インターロイキン6; 滑膜細胞

1. Inhibitory effects of anti-interleukin-6 receptor antibody (anti-IL-6R Ab) against murine and similar collagen-induced arthritis and joint destruction were elucidated.2. Humanized anti-IL-6R Ab was proven to be effective to patients with refractory rheumatoid arthritis (RA) and thus confirming that IL-6 plays a major role in the RA pathology. It also shows IL-6 signal blocking can be a new therapy for RA.3. IL-6 in the presence of soluble IL-6R (sIL-6R) inhibits the growth of synovial cells. TNFα-induced IL-6 can be a negative feedback factor of TNFα-induced synovial cell proliferation in RA.4. Therapeutic effects of IL-6 blockade were through elimination of inflammatory cell penetrating the RA synovial tissue and also through inhibition of angiogenesis and osteoclast formation.5. STATs-induced STATs inhibitor-1 and its family molecule SSI-3 as negative feed back factors of intracytoplasmic IL-6 signaling may be involved in the chronic inflammatory status of RA.6. These results indicate the possibility of new therapeutic approach for RA by blocking IL-6 signaling based on the pathophysiology of RA.

1.阐明了抗白细胞介素6受体抗体(anti-IL-6R Ab)对小鼠及类似胶原诱导的关节炎和关节破坏的抑制作用。2．人源化抗 IL-6R Ab 被证明对难治性类风湿性关节炎 (RA) 患者有效，从而证实 IL-6 在 RA 病理学中发挥着重要作用。它还表明 IL-6 信号阻断可以成为 RA.3 的新疗法。可溶性 IL-6R (sIL-6R) 存在下的 IL-6 会抑制滑膜细胞的生长。 TNFα诱导的IL-6可能是RA.4中TNFα诱导的滑膜细胞增殖的负反馈因子。 IL-6阻断的治疗作用是通过消除穿透RA滑膜组织的炎症细胞以及抑制血管生成和破骨细胞形成来实现的。5． STATs诱导的STATs抑制因子1及其家族分子SSI-3作为胞质内IL-6信号的负反馈因子可能参与RA的慢性炎症状态。6。这些结果表明基于 RA 的病理生理学，通​​过阻断 IL-6 信号传导来治疗 RA 的新方法的可能性。

项目成果

Matsue H., T. Sakakibara, R. Matsuwaka, M. Mitsuno, M. Tsujimoto, N. Nishimoto: "Malignant fibrous histiocytoma of the heart producing Interleukin-6"Journal of Thoracic & Cardiovascular Surgery. 116. 522-524 (1998)

Matsue H.、T. Sakakibara、R. Matsuwaka、M. Mitsuno、M. Tsujimoto、N. Nishimoto：“产生白细胞介素 6 的心脏恶性纤维组织细胞瘤”胸科杂志

Nishimoto N., Yoshizaki K., and Kishimoto T.: "Anticytokine therapy in autoimmune diseases"Internal Medicine. 38. 178-182 (1999)

Nishimoto N.、Yoshizaki K. 和 Kishimoto T.：“自身免疫性疾病中的抗细胞因子治疗”内科。

吉崎和幸,西本憲弘: "Moleculra Medicin臨時増刊号症候・病態のメカニズム.骨融解像."中山書店. 606 (1998)

Kazuyuki Yoshizaki、Norihiro Nishimoto：“分子医学症状和病理学特刊机制。骨溶解图像。”606 (1998)。

Nishimoto, N., K. Yoshizaki, and T. Kishimoto.: "Anticytokine therapy in autoimmune diseases."Internal. Med.. 38. 178-182 (1999)

Nishimoto, N.、K. Yoshizaki 和 T. Kishimoto.：“自身免疫性疾病中的抗细胞因子治疗”。内部。

Nishimoto N., and K. Yoshizaki.: "Anti-IL-6 receptor therapy for rheumatoid arthritis."Riumachi-ka. 19. 399-402 (1998)

Nishimoto N. 和 K. Yoshizaki.：“类风湿性关节炎的抗 IL-6 受体疗法。”Riumachi-ka。