IL-18 in rheumatoid inflammation and angiogenesis
IL-18 in rheumatoid inflammation and angiogenesis
批准号:
7279466
负责人:
ALISA E KOCH
金额:
$24.67万
依托单位国家:
美国
项目类别:
财政年份:
2003
资助国家:
美国
项目状态:
已结题
起止时间:
2003-09-01 至 2010-08-31
关键词:
AnimalsArthritisBiological AssayBlood VesselsBreedingCell AdhesionCell Adhesion MoleculesCellsClassConditionDevelopmentDiseaseE-SelectinEndothelial CellsFibroblastsGTP-Binding ProteinsGenesGranulomaGrowthHumanInfiltrationInflammationInflammatoryIntegrinsInterleukin-1Interleukin-18InterleukinsJointsLeukocytesMediatingMediator of activation proteinMethodsMitogen-Activated Protein KinasesMitogensMusPharmaceutical PreparationsPhosphatidylinositolsPhosphotransferasesPoriferaProductionProtein-Serine-Threonine KinasesRheumatoid ArthritisRoleSignal PathwaySignal TransductionSiteSynovial FluidT-LymphocyteTherapeuticTissuesTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1Wild Type Mouseangiogenesisanimal breedingchemokinecytokinedayin vivo Modelmatrigelnovelprototyperesearch studysrc-Family Kinasestherapeutic target
中文摘要
描述(由申请人提供):
英文摘要
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.
期刊论文(7)
专著(0)
科研奖励(0)
会议论文
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
影响因子:
--
作者:
[Rabquer,BradleyJ, Hou,Yong, Ruth,JeffreyH, Luo,Wei, Eitzman,DanielT, Koch,AlisaE, Amin,MohammadA]
通讯作者:
Amin,MohammadA
DOI:
10.1002/art.34336
发表时间:
2012-06
期刊:
ARTHRITIS AND RHEUMATISM
影响因子:
--
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.
Fucosyl transferases in inflammation and angiogenesis
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批准号:8394606
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2009
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负责人:ALISA E KOCH
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依托单位:
Fucosyl transferases in inflammation and angiogenesis
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批准号:8195409
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项目类别:
-
资助金额:$0.0万
-
财政年份:2009
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负责人:ALISA E KOCH
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依托单位:
Fucosyl transferases in inflammation and angiogenesis
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批准号:7797230
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项目类别:
-
资助金额:$0.0万
-
财政年份:2009
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负责人:ALISA E KOCH
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依托单位:
Fucosyl transferases in inflammation and angiogenesis
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批准号:7905690
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项目类别:
-
资助金额:$0.0万
-
财政年份:2009
-
负责人:ALISA E KOCH
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依托单位:
IL-18 in rheumatoid inflammation and angiogenesis
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批准号:6941299
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项目类别:
-
资助金额:$28.45万
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财政年份:2003
-
负责人:ALISA E KOCH
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依托单位:
IL-4 and IL-13 gene therapy for arthritis
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批准号:6677864
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项目类别:
-
资助金额:$8.82万
-
财政年份:2003
-
负责人:ALISA E KOCH
-
依托单位:
IL-18 in rheumatoid inflammation and angiogenesis
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批准号:6799261
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项目类别:
-
资助金额:$28.49万
-
财政年份:2003
-
负责人:ALISA E KOCH
-
依托单位:
IL-4 and IL-13 gene therapy for arthritis
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批准号:7012753
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项目类别:
-
资助金额:$25.79万
-
财政年份:2003
-
负责人:ALISA E KOCH
-
依托单位:
IL-18 in rheumatoid inflammation and angiogenesis
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批准号:7118620
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项目类别:
-
资助金额:$25.42万
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财政年份:2003
-
负责人:ALISA E KOCH
-
依托单位:
IL-4 and IL-13 gene therapy for arthritis
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批准号:6805525
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项目类别:
-
资助金额:$26.45万
-
财政年份:2003
-
负责人:ALISA E KOCH
-
依托单位:
IL-18 in rheumatoid inflammation and angiogenesis
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批准号:6606731
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项目类别:
-
资助金额:$28.51万
-
财政年份:2003
-
负责人:ALISA E KOCH
-
依托单位:
IL-4 and IL-13 gene therapy for arthritis
-
批准号:6850110
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项目类别:
-
资助金额:$26.43万
-
财政年份:2003
-
负责人:ALISA E KOCH
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依托单位:
NOVEL ANGIOGENIC CYTOKINE INDUCED ENDOTHELIAL ANTIGEN
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批准号:6184343
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项目类别:
-
资助金额:$20.72万
-
财政年份:1999
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负责人:ALISA E KOCH
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依托单位:
NOVEL ANGIOGENIC CYTOKINE INDUCED ENDOTHELIAL ANTIGEN
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批准号:6797589
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项目类别:
-
资助金额:$21.32万
-
财政年份:1999
-
负责人:ALISA E KOCH
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依托单位:
NOVEL ANGIOGENIC CYTOKINE INDUCED ENDOTHELIAL ANTIGEN
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批准号:6389718
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项目类别:
-
资助金额:$21.34万
-
财政年份:1999
-
负责人:ALISA E KOCH
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依托单位:
NOVEL ANGIOGENIC CYTOKINE INDUCED ENDOTHELIAL ANTIGEN
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批准号:6527120
-
项目类别:
-
资助金额:$0.67万
-
财政年份:1999
-
负责人:ALISA E KOCH
-
依托单位:
NOVEL ANGIOGENIC CYTOKINE INDUCED ENDOTHELIAL ANTIGEN
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批准号:2744791
-
项目类别:
-
资助金额:$21.91万
-
财政年份:1999
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负责人:ALISA E KOCH
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依托单位:
IL 4 AND IL 13 GENE THERAPY FOR ARTHRITIS
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批准号:2887396
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项目类别:
-
资助金额:$20.7万
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财政年份:1998
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负责人:ALISA E KOCH
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依托单位:
IL 4 AND IL 13 GENE THERAPY FOR ARTHRITIS
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批准号:2486987
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项目类别:
-
资助金额:$12.05万
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财政年份:1998
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负责人:ALISA E KOCH
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依托单位:
IL 4 AND IL 13 GENE THERAPY FOR ARTHRITIS
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批准号:6169972
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项目类别:
-
资助金额:$21.3万
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财政年份:1998
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负责人:ALISA E KOCH
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依托单位:
国内基金
海外基金
Autoimmune diseases therapies: variations on the microbiome in rheumatoid arthritis
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批准号:31171277
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项目类别:面上项目
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资助金额:60.0万元
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批准年份:2011
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负责人:Christine Nardini
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依托单位:
Molecular Interaction Reconstruction of Rheumatoid Arthritis Therapies Using Clinical Data
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批准号:31070748
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项目类别:面上项目
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资助金额:34.0万元
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批准年份:2010
-
负责人:Christine Nardini
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依托单位: