Differentiation of Granulocytes and Macrophages
粒细胞和巨噬细胞的分化
基本信息
- 批准号:7470017
- 负责人:
- 金额:$ 23.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1978
- 资助国家:美国
- 起止时间:1978-03-01 至 2010-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAgonistAnimalsAutoimmunityAutomobile DrivingBiologyBlood CellsBone Marrow TransplantationCISH geneCSF3 geneCell LineageCellsCellular biologyChemotherapy-Oncologic ProcedureCommunicable DiseasesConditionCytokine Inducible SH2-Containing ProteinCytokine ReceptorsCytokine SignalingDevelopmentDiseaseFamily memberFeedbackFunctional disorderGenerationsGenesGenetic TranscriptionGoalsHematological DiseaseHematopoiesisHematopoieticHemorrhageHomeostasisHost DefenseIn VitroInfectionInflammationInflammatoryInflammatory ResponseInterleukin-6InterventionKnockout MiceKnowledgeMalignant NeoplasmsMeasuresMediatingMolecularMolecular TargetMouse StrainsMusMutationMyeloid Progenitor CellsPathologyPathway interactionsPhosphotransferasesPhysiologicalPlayPositioning AttributeProcessProductionProgress ReportsProteinsReactionReagentReceptor Cross-TalkRelative (related person)Research PersonnelRoleScreening procedureSignal PathwaySignal TransductionSignaling ProteinSpecificityStressSuppressor of Cytokine Signaling Family ProteinSystemTherapeutic Usesbasecell typecytokineembryonic stem cellextracellulargranulocytein vivoinhibitor/antagonistmacrophageneutrophilpreventprogramsreceptorresearch studyresponsetherapeutic targettranscription factor
项目摘要
DESCRIPTION (provided by applicant): Cytokine-activated signaling pathways are the key determinants of the production, differentiation and state of functional activation of hematopoietic cells involved in host defense and inflammatory reactions. These pathways include both positive signaling intermediates (including kinases and latent transcription factors) and negative feedback pathways that limit the responses of cells to those appropriate to the situation. Our discovery of the Suppressor of Cytokine Signaling (SOCS) family of proteins and determination of their physiological importance using specific gene-deleted mice has identified these proteins as key inhibitors of excessive inflammatory responses in vivo. In particular, SOCS3 was shown to be the critical SOCS protein inhibiting the formation and function of granulocytes and macrophages in response to cytokines like G-CSF and IL-6 and to have a previously unsuspected role in maintaining the appropriate specificity in cellular responses to these cytokines. We have generated several important reagents including genetically modified mice where the roles of SOCS3 in specific cell types and the roles of specific domains in SOCS3 or the corresponding receptors can be determined at the whole animal, cellular and molecular levels. The major questions to be answered are: How do the different domains of SOCS3 interact with different intracellular components to mediate signal suppression? How does SOCS3 determine the specificity of the signaling pathways from these cytokines? Which hematopoietic and non-hematopoietic cells are affected by the actions of SOCS3 and what are their relative contributions to the inflammatory response? Do other SOCS proteins, at least to some extent, have similar actions to SOCS3 on hematopoietic cells? Answering these questions will allow us to define more clearly those disease conditions (inflammation, autoimmunity, infections, bone marrow transplantation for cancer chemotherapy) that would benefit from the use of SOCS3 agonists or antagonists as well as defining the best molecular targets to use for their screening.
描述(由申请人提供):细胞因子激活的信号通路是参与宿主防御和炎症反应的造血细胞的产生、分化和功能激活状态的关键决定因素。这些途径包括正信号中间体(包括激酶和潜在的转录因子)和负反馈途径,这些途径限制了细胞对那些适合情况的反应。我们发现了细胞因子信号传导抑制因子(SOCS)家族蛋白质,并使用特定基因缺失小鼠确定了它们的生理重要性,已将这些蛋白质鉴定为体内过度炎症反应的关键抑制剂。特别地,SOCS 3被证明是抑制响应于细胞因子如G-CSF和IL-6的粒细胞和巨噬细胞的形成和功能的关键SOCS蛋白,并且在维持对这些细胞因子的细胞应答的适当特异性中具有先前未被怀疑的作用。我们已经产生了几种重要的试剂,包括转基因小鼠,其中SOCS 3在特定细胞类型中的作用以及SOCS 3或相应受体中特定结构域的作用可以在整个动物,细胞和分子水平上确定。需要回答的主要问题是:SOCS 3的不同结构域如何与不同的细胞内组分相互作用以介导信号抑制?SOCS 3如何决定这些细胞因子信号通路的特异性?哪些造血细胞和非造血细胞受到SOCS 3作用的影响,它们对炎症反应的相对贡献是什么?其他SOCS蛋白是否至少在某种程度上与SOCS 3对造血细胞有类似的作用?阐明这些问题将使我们能够更清楚地定义那些将受益于使用SOCS 3激动剂或拮抗剂的疾病状况(炎症、自身免疫、感染、骨髓移植用于癌症化疗),以及定义用于其筛选的最佳分子靶点。
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)
专利数量(0)
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DONALD METCALF其他文献
DONALD METCALF的其他文献
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{{ truncateString('DONALD METCALF', 18)}}的其他基金
SELF-RENEWAL IN NORMAL & LEUKEMIC HEMOPOIETIC STEM CELLS
正常情况下的自我更新
- 批准号:
3167126 - 财政年份:1983
- 资助金额:
$ 23.04万 - 项目类别:
SELF-RENEWAL IN NORMAL/LEUKEMIC HEMOPOIETIC STEM CELLS
正常/白血病造血干细胞的自我更新
- 批准号:
3167122 - 财政年份:1983
- 资助金额:
$ 23.04万 - 项目类别:
SELF-RENEWAL IN NORMAL & LEUKEMIC HEMOPOIETIC STEM CELLS
正常情况下的自我更新
- 批准号:
3167125 - 财政年份:1983
- 资助金额:
$ 23.04万 - 项目类别:
SELF-RENEWAL IN NORMAL & LEUKEMIC HEMOPOIETIC STEM CELLS
正常情况下的自我更新
- 批准号:
3167120 - 财政年份:1983
- 资助金额:
$ 23.04万 - 项目类别:
SELF RENEWAL IN NORMAL & LEUKEMIC HEMOPOIETIC STEM CELLS
正常情况下的自我更新
- 批准号:
3167119 - 财政年份:1983
- 资助金额:
$ 23.04万 - 项目类别:
SELF RENEWAL IN NORMAL & LEUKEMIC HEMOPOIETIC STEM CELLS
正常情况下的自我更新
- 批准号:
3167123 - 财政年份:1983
- 资助金额:
$ 23.04万 - 项目类别:
SELF RENEWAL IN NORMAL & LEUKEMIC HEMOPOIETIC STEM CELLS
正常情况下的自我更新
- 批准号:
3167124 - 财政年份:1983
- 资助金额:
$ 23.04万 - 项目类别:
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