IL-18 in rheumatoid inflammation and angiogenesis

IL-18 在类风湿炎症和血管生成中的作用

• 批准号: 7279466
• 负责人: ALISA E KOCH
• 金额: $ 24.67万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7279466
• 关键词: Animals; Arthritis; Biological Assay; Blood Vessels; Breeding; Cell Adhesion; Cell Adhesion Molecules; Cells; Class; Condition; Development; Disease; E-Selectin; Endothelial Cells; Fibroblasts; GTP-Binding Proteins; Genes; Granuloma; Growth; Human; Infiltration; Inflammation; Inflammatory; Integrins; Interleukin-1; Interleukin-18; Interleukins; Joints; Leukocytes; Mediating; Mediator of activation protein; Methods; Mitogen-Activated Protein Kinases; Mitogens; Mus; Pharmaceutical Preparations; Phosphatidylinositols; Phosphotransferases; Porifera; Production; Protein-Serine-Threonine Kinases; Rheumatoid Arthritis; Role; Signal Pathway; Signal Transduction; Site; Synovial Fluid; T-Lymphocyte; Therapeutic; Tissues; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Wild Type Mouse; angiogenesis; animal breeding; chemokine; cytokine; day; in vivo Model; matrigel; novel; prototype; research study; src-Family Kinases; therapeutic target

DESCRIPTION (provided by applicant): Rheumatoid arthritis (RA) is a prototype inflammatory disease characterized by leukocyte infiltration, which is in large part mediated by chemokines and cellular adhesion molecules. Angiogenesis, or new blood vessel growth, is integral to the development of the inflamed RA synovial tissue (ST) pannus. Without angiogenesis, leukocyte infiltration could not occur. A novel cytokine, interleukin (IL)-I8 has recently been identified. This cytokine stimulates T helper 1 (Thl) cytokine production by T cells. The functional role of this cytokine in RA is still unclear. In this proposal we hypothesize that IL-18 contributes to RA joint inflammation and angiogenesls. We plan to determine the mechanism by which IL-18 serves as an inducer of chemokine production in RA ST fibroblasts and whether this chemokine production occurs via G proteins, src family kinases, mitogen activated kinases, or PI3 kinases. Besides chemokines, cellular adhesion molecules are needed for leukocyte ingress into inflamed STs. We will examine whether IL-18 induces leukocyte-endothelial adhesion molecule expression and the mechanism of this expression. Finally, leukocyte ingress would not take place without angiogenesis. We will ascertain the mechanism by which IL-18 mediates angiogenesis in RA in terms of the endothelial signaling pathways, which are activated. Finally, we will study IL-18 gene-deficient mice to determine if they have impaired angiogenesis. We will employ these gene deficient animals bred on an arthritis-susceptible strain to examine whether arthritis associated angiogenesis in the joints is decreased. Several years ago cytokine modulation as a therapy for RA was simply a hope. Currently, cytokine modulation aimed at ablating tumor necrosis factor-alpha is one of the best treatments available for RA and IL-1 targeting is beginning to be used therapeutically. IL-18, by virtue of its ability to induce chemokine release, adhesion molecule expression, and angiogenesis, appears to be a very critical cytokine to target. Our proposal should answer some key questions, which may determine the ability of IL-18 to be a therapeutic target in RA.

描述（由申请人提供）：

项目成果

New insights in synovial angiogenesis.

• DOI: 10.1016/j.jbspin.2009.05.011
• 发表时间: 2010-01
• 期刊: JOINT BONE SPINE
• 影响因子: 4.2
• 作者: Szekanecz, Zoltan;Besenyei, Timea;Paragh, Gyoergy;Koch, Alisa E.
• 通讯作者: Koch, Alisa E.

H-2g, a glucose analog of blood group H antigen, mediates monocyte recruitment in vitro and in vivo via IL-8/CXCL8.

H-2g 是 H 型血抗原的葡萄糖类似物，通过 IL-8/CXCL8 在体外和体内介导单核细胞募集。

• DOI: 10.2147/oarrr.s36163
• 发表时间: 2012
• 期刊: Open access rheumatology : research and reviews
• 作者: Rabquer,BradleyJ;Hou,Yong;Ruth,JeffreyH;Luo,Wei;Eitzman,DanielT;Koch,AlisaE;Amin,MohammadA
• 通讯作者: Amin,MohammadA

Effect of oxidative stress on protein tyrosine phosphatase 1B in scleroderma dermal fibroblasts.

• DOI: 10.1002/art.34336
• 发表时间: 2012-06
• 期刊: ARTHRITIS AND RHEUMATISM
• 作者: Tsou, Pei-Suen;Talia, Nadine N.;Pinney, Adam J.;Kendzicky, Ann;Piera-Velazquez, Sonsoles;Jimenez, Sergio A.;Seibold, James R.;Phillips, Kristine;Koch, Alisa E.
• 通讯作者: Koch, Alisa E.