Role Of Monocytes In Immunopathology

单核细胞在免疫病理学中的作用

• 批准号: 6501687
• 负责人: LARRY M WAHL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6501687
• 关键词: atherosclerosis; biological signal transduction; clinical research; enzyme activity; enzyme induction /repression; human subject; human tissue; immunopathology; metalloendopeptidases; monocyte; tissue /cell culture; tissue inhibitor of metalloproteinases

The primary focus of our research is to define the factors and signal transduction pathways involved in the modulation of human monocyte functions that may contribute to the immunopathology associated with various disease states. Connective tissue destruction is associated with many diseases in which the monocyte/macrophage is a prominent cell. Since matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are believed to play a major role in the destruction and remodeling of connective tissue, a major emphasis has been placed on how these enzymes and inhibitors are regulated. To address this question we are examining how biological mediators, such as cytokines, lipids and gram-negative bacterial, influence the mitogen-activated protein kinase and cyclooxygenase pathways involved in monocytge MMP and TIMP production. Current studies on the role of monocyte MMPs in various diseases have examined (a) how monocyte MT1-MMP may influence tumor metastasis through the activation of MMP-2 and (b) the impact of lipids, such as LDL and HDL, on monocyte MMP production as it relates to the immunopathology associated with atherosclerosis.

我们研究的主要重点是定义参与人类单核细胞功能调节的因素和信号转导途径，这可能有助于与各种疾病状态相关的免疫病理学。结缔组织破坏与单核细胞/巨噬细胞是突出细胞的许多疾病有关。由于基质金属蛋白酶（MMP）和MMPS（TIMP）的组织抑制剂被认为在结缔组织的破坏和重塑中起主要作用，因此已经将这些酶和抑制剂调节的主要重点放在了。为了解决这个问题，我们正在研究生物学介质（例如细胞因子，脂质和革兰氏阴性细菌）如何影响有丝分裂原激活的蛋白激酶和环氧酶途径参与单层面部MMP和TIMP的产生。目前关于单核细胞MMP在各种疾病中的作用的研究（a）（a）（a）单核细胞MT1-MMP如何通过激活MMP-2和（b）脂质的影响（例如LDL和HDL）对单核细胞MMP的产生，对与免疫病学相关的单核细胞MMP产生，如何影响肿瘤转移。