possible therapeutic application of gene therapy of anti-inflammatory cytokines to rheumatoid joint destruction

抗炎细胞因子基因疗法对类风湿性关节破坏的可能治疗应用

• 批准号: 17591557
• 负责人: SUGIYAMA Eiji
• 金额: $ 2.18万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591557/
• 关键词: Rheumatoid arthritis; osteoclast; c-Fos; adeno-associated virus; interleukin-4; Interleukin-10; PPARγ agonists; TNFα; インターロイキン4; 遺伝子療法

Rheumatoid Arthritis (RA) is characterized by destruction of joint cartilage and bone, and osteoclasts are the principal cell type responsible for bone resorption in RA. Therefore, osteoclasts are real targets for the treatment of RA. In this study, we found that IL-4 and IL-10, anti-inflammatory cytokines, inhibited osteoclast differentiation via suppression of c-Fos in murine bone marrow cells. In addition, we showed that adeno-associated virus vector of IL-4 (AAV-IL-4) efficiently infected monocytes, precursor of osteoclasts, and that AAV-IL-4 inhibited TNFα-mediated osteoclastogenesis from human peripheral monocytes, suggesting that AAV-IL-4 gene therapy may be a promising therapeutic applicant for RA. Furthermore, we demonstrated that agonists of peroxisome proliferator-activated receptor γ (PPARγ), a new class of anti-inflammatory compounds, inhibited TNFα-mediated osteoclasts generation in human monocytes, and the inhibitory effect may be mediated in part by suppression of monocyte chemoattractant-1 (MCP-1). In summary, we proposed two types of therapeutic strategy, AAV-IL-4 gene therapy and PPARγ agonist, for rheumatoid joint destruction. We hope this project may contribute to the development of anti-rheumatic drugs.

类风湿关节炎（RA）的特征是关节软骨和骨骼的破坏，破骨细胞是负责RA骨骼分辨率的主要细胞类型。因此，破骨细胞是治疗RA的真正靶标。在这项研究中，我们发现抗炎细胞因子IL-4和IL-10通过在鼠骨髓细胞中抑制C-FOS抑制破骨细胞的分化。 In addition, we showed that adeno-associated virus vector of IL-4 (AAV-IL-4) effectively infected monocytes, precursor of osteoclasts, and that AAV-IL-4 inhibited TNFα-mediated osteoclastogenesis from human peripheral monocytes, suggesting that AAV-IL-4 gene therapy may be a promising therapeutic applicant for RA.此外，我们证明了过氧化物体增生剂的激动剂γ（PPARγ）（PPARγ）是一类新的抗炎性化合物，抑制TNFα介导的人类单核细胞中的骨细胞的产生，抑制作用可以通过抑制作用，可以通过抑制作用的单粒型单核teblectecyte Chemocyte Chemocyte Chemocateant-1（McPpp）介导。总而言之，我们提出了两种类型的理论，即AAV-IL-4基因疗法和PPARγ激动剂，用于类风湿的关节破坏。我们希望该项目可能有助于抗风险药物的发展。

项目成果

アデノ随伴ウイルスベクターを用いたIL-4遺伝子導入によるヒト破骨細胞分化抑制効果に関する検討

使用腺相关病毒载体导入IL-4基因抑制人破骨细胞分化效果的研究

• 发表时间: 2006
• 作者: Hounoki H;Sugiyama E;Mohamed SG;Shinoda K;Taki H;Abdel-Aziz HO;Maruyama M;Kobayashi M;Miyahara T;朴木 博幸;杉山 英二;Hounaki H;Sugiyama E;朴木 博幸
• 通讯作者: 朴木 博幸

Isoproterenol suppresses cytokine-induced RANTES secretion in human lung epithelial cells through the inhibition of c-jun N-terminal kinase pathway

• DOI: 10.1016/j.bbrc.2006.09.117
• 发表时间: 2006-11-24
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Miyabayashi, Koutarou;Maruyama, Muneharu;Kobayashi, Masashi
• 通讯作者: Kobayashi, Masashi

15-d-PGJ2はTNFαに串るヒト単球の破骨細胞誘導を抑制する

15-d-PGJ2 通过 TNFα 抑制人单核细胞的破骨细胞诱导

• 发表时间: 2006
• 作者: Hounoki H;Sugiyama E;Mohamed SG;Shinoda K;Taki H;Abdel-Aziz HO;Maruyama M;Kobayashi M;Miyahara T;朴木 博幸;杉山 英二;Hounaki H;Sugiyama E;朴木 博幸;杉山 英二
• 通讯作者: 杉山 英二

Interleukin-10 inhibits RANKL-mediated expression of NFATcl in part via suppression of c-Fos and c-Jun in RAW264.7 cells and mouse bone marrow cells

Interleukin-10 部分通过抑制 RAW264.7 细胞和小鼠骨髓细胞中的 c-Fos 和 c-Jun 来抑制 RANKL 介导的 NFATcl 表达

• 发表时间: 2007
• 期刊: Bone 41
• 作者: Mohamed SG;et. al.
• 通讯作者: et. al.

Adeno-associated virus vector-mediated gene transfer of IL-4 inhibits TNFα-mediated osteoclastogenesis in human monocytes.

腺相关病毒载体介导的 IL-4 基因转移抑制人单核细胞中 TNFα 介导的破骨细胞生成。

• 发表时间: 2006
• 作者: Hounoki H;Sugiyama E;Mohamed SG;Shinoda K;Taki H;Abdel-Aziz HO;Maruyama M;Kobayashi M;Miyahara T;朴木 博幸;杉山 英二;Hounaki H;Sugiyama E;朴木 博幸;杉山 英二;Sugiyama E;Hounoki H
• 通讯作者: Hounoki H