Roles of MIF and iNOS in SLE-associate inflammation
MIF 和 iNOS 在 SLE 相关炎症中的作用
基本信息
- 批准号:6948780
- 负责人:
- 金额:$ 24.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-09-10 至 2008-06-30
- 项目状态:已结题
- 来源:
- 关键词:Australiacell adhesion moleculescell cell interactioncell migrationdisease /disorder modelfluorescence microscopygenetically modified animalsinflammationintravital microscopylaboratory mouseleukocytesmicrocirculationmigration inhibition factornitric oxidenitric oxide synthasepathologic processsystemic lupus erythematosusvascular endothelium
项目摘要
DESCRIPTION (provided by applicant):
Diverse inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) share the manifestation of organ injury induced by activation of inflammatory pathways. A feature common to inflammatory diseases is the infiltration into tissues of blood-derived leukocytes, a phenomenon that requires specific leukocyte-endothelial cell interactions in the microcirculation. While many molecules important in leukocyte-endothelial interactions have been identified, the specific events operative in the recruitment of leukocytes to target organs remain incompletely understood. A greater understanding of these pathways has the potential to lead to the discovery of novel, specific, yet broad-spectrum therapeutic modalities. For example, it is unclear whether distinct leukocyte-endothelial interactions are operative in rheumatic diseases, or indeed in mediating the distinct organ manifestations in these diseases. Complete characterization of the mechanisms of leukocyte recruitment requires the direct examination of leukocyte-endothelial interactions in vivo. This is possible using the technique of intravital microscopy (IVM), which has now been applied to many tissues including skin, brain, and synovium. Strong preliminary data suggests the involvement of mediators such as nitric oxide (NO) and the cytokine macrophage migration inhibitory factor (MIF) in the modulation of leukocyte-endothelial interactions. The long-term objectives of this project are to expand understanding of the role of these and other mediators in the microcirculation in models of SLE and RA. The specific aims of this project are to:
(i) Examine the leukocyte-endothelial interactions in the pathogenesis of murine SLE. Using IVM, we will define the regulatory role of NO in the MRL/fas-lpr model of SLE.
(ii) Examine the role of MIF in the regulation of leukocyte-endothelial interactions. WT and MIF-/- mice, as well as mice treated with anti-MIF mAb and recombinant MIF will be studied using IVM of the synovial and muscle microcirculations under conditions of antigen-driven inflammation.
(iii) Examine the role of MIF in the modulation of leukocyte-endothelial interactions in the pathogenesis of murine SLE. Using rMIF, anti-MIF mAb, and anti-MIF small molecules, and by generating MRL/Ipr/MIF -/- mice, we will examine the role of MIF in the modulation of leukocyte-endothelial interactions in murine SLE.
描述(由申请人提供):
系统性红斑狼疮(SLE)和类风湿性关节炎(RA)等多种炎症性疾病都有一个共同的表现,即炎症通路的激活导致器官损伤。炎症性疾病的一个共同特征是血液来源的白细胞浸润到组织中,这是一种需要微循环中特定白细胞-内皮细胞相互作用的现象。虽然许多分子在白细胞-内皮细胞相互作用中起重要作用,但在白细胞向靶器官募集中起作用的特定事件仍不完全清楚。对这些途径的更深入了解有可能导致发现新的,特异性的,但广谱的治疗方式。例如,目前还不清楚不同的白细胞-内皮细胞相互作用是否在风湿性疾病中起作用,或者确实介导这些疾病中不同的器官表现。白细胞募集机制的完整表征需要直接检查体内白细胞-内皮细胞相互作用。使用活体显微镜(IVM)技术可以实现这一点,该技术现已应用于许多组织,包括皮肤、大脑和滑膜。强有力的初步数据表明,介体,如一氧化氮(NO)和细胞因子巨噬细胞迁移抑制因子(MIF)在白细胞-内皮细胞相互作用的调制的参与。该项目的长期目标是扩大对这些和其他介质在SLE和RA模型微循环中的作用的理解。该项目的具体目标是:
(i)研究小鼠SLE发病机制中的白细胞-内皮细胞相互作用。使用IVM,我们将确定NO在SLE的MRL/fas-lpr模型中的调节作用。
(ii)检查MIF在调节白细胞-内皮细胞相互作用中的作用。WT和MIF-/-小鼠以及用抗MIF mAb和重组MIF处理的小鼠将在抗原驱动的炎症条件下使用滑膜和肌肉微循环的IVM进行研究。
(iii)研究MIF在调节小鼠SLE发病机制中白细胞-内皮细胞相互作用中的作用。使用rMIF、抗MIF mAb和抗MIF小分子,并通过产生MRL/Ipr/MIF -/-小鼠,我们将研究MIF在调节小鼠SLE中白细胞-内皮细胞相互作用中的作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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{{ truncateString('MICHAEL J HICKEY', 18)}}的其他基金
Roles of MIF and iNOS in SLE-associate inflammation
MIF 和 iNOS 在 SLE 相关炎症中的作用
- 批准号:
7099569 - 财政年份:2004
- 资助金额:
$ 24.57万 - 项目类别:
Roles of MIF and iNOS in SLE-associate inflammation
MIF 和 iNOS 在 SLE 相关炎症中的作用
- 批准号:
7247274 - 财政年份:2004
- 资助金额:
$ 24.57万 - 项目类别:
Roles of MIF and iNOS in SLE-associate inflammation
MIF 和 iNOS 在 SLE 相关炎症中的作用
- 批准号:
6840308 - 财政年份:2004
- 资助金额:
$ 24.57万 - 项目类别:
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