Control of airway remodeling by TNFR family molecules
TNFR家族分子对气道重塑的控制
基本信息
- 批准号:8381193
- 负责人:
- 金额:$ 45.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-09-01 至
- 项目状态:未结题
- 来源:
- 关键词:AcuteAllergensAllergicAsthmaAutomobile DrivingBreathingCell Differentiation processCellsCharacteristicsChronicClinicalCollagenComplementDataDepositionDevelopmentDiseaseEpithelialEpithelial CellsEpitheliumEventExposure toExtracellular Matrix ProteinsFamilyFamily memberFibroblastsFibronectinsFibrosisGoalsHumanHyperplasiaImmuneImmune responseInfectionInfection preventionInfiltrationInflammationInflammatoryInstructionKnowledgeLamininLeadLeucocytic infiltrateLigandsLightLinkLungLung InflammationLymphocyteMediatingMesenchymalMetaplasiaModelingMolecularMucous body substanceMusPathogenesisPathway interactionsPatientsPattern recognition receptorPhasePredispositionProcessProductionProteinsRegulationRhinovirusRoleSamplingSatellite VirusesSeveritiesSignal TransductionSmooth MuscleSmooth Muscle Actin Staining MethodSourceSpecimenStimulusSurfaceT-LymphocyteTGFB1 geneTNFSF4 geneTenascinTestingTh2 CellsTherapeutic InterventionTumor Necrosis Factor ReceptorTumor Necrosis Factor-alphaVirusairborne allergenairway inflammationairway remodelingangiogenesisasthmatic patientbronchial epitheliumcell typeeosinophilhigh voltage electron microscopyhuman datalymphotoxin beta receptormacrophagemast cellmembermuscle formmuscle hypertrophynovelpathogenreceptorthought control
项目摘要
PROJECT SUMMARY (See instructions):
The allergic form of asthma is driven by an immune response to airborne allergens, and can be exacerbated by a number of factors including exposure to viruses. A typical signature of disease is the accumulation in the lungs of Th2 lymphocytes, eosinophils, mast cells, fibroblasts, and macrophages. Whereas the acute phase of asthma is characterized largely by rapid cell infiltration in the lungs, chronic asthma is characterized
by progressive airway remodeling which includes epithelial cell mucus metaplasia, smooth muscle hypertrophy/hyperplasia, subepithelial fibrosis, and increased angiogenesis. Fibrosis is due to deposition of extracellular matrix proteins such as collagen, fibronectin, tenascin, and laminin, thought produced largely from differentiating fibroblasts or epithelial cells, which can additionally be induced to express alpha smooth
muscle actin and contribute to the enhanced smooth muscle mass. How all of these cell types are controlled is largely unknown. This proposal will focus on several members of the tumor necrosis factor (TNF) and TNF receptor superfamily, and test the hypotheses that OX40 (CD134) interacting with OX40L (CD252), and LIGHT (CD258) interacting with two receptors, HVEM (CD270) and LTBR (lymphotoxin beta receptor), are
signatures of allergen-induced inflammation and remodeling in lungs of patients with varying severity of asthma; that these molecules will be further induced in the lungs of patients that are exposed to rhinovirus, a pathogen that has been associated with asthma exacerbations; and that they will be functionally relevant to the inflammatory and remodeling activities of bronchial epithelial cells, and lung macrophages, fibroblasts,
and T cells. The treatment options for asthmatics are currently limited. Understanding when and where these TNF/TNFR family molecules are expressed, and the functional activities that result from their interactions, might lead to new and novel targets for therapeutic intervention in both acute and chronic asthma.
项目总结(见说明):
过敏性哮喘是由对空气中过敏原的免疫反应驱动的,并且可以由包括暴露于病毒在内的许多因素加剧。疾病的典型特征是Th 2淋巴细胞、嗜酸性粒细胞、肥大细胞、成纤维细胞和巨噬细胞在肺中的积累。尽管哮喘的急性期主要特征在于肺中的快速细胞浸润,但慢性哮喘的特征在于
进行性气道重塑,包括上皮细胞粘液化生、平滑肌肥大/增生、上皮下纤维化和血管生成增加。纤维化是由于细胞外基质蛋白如胶原蛋白、纤连蛋白、腱生蛋白和层粘连蛋白的沉积,这些蛋白被认为主要是由分化的成纤维细胞或上皮细胞产生的,其可以另外被诱导表达α平滑蛋白。
肌肉肌动蛋白,并有助于增强平滑肌质量。所有这些细胞类型是如何被控制的在很大程度上是未知的。本研究主要针对肿瘤坏死因子(TNF)和TNF受体超家族的几个成员,并对OX 40(CD 134)与OX 40 L(CD 252)相互作用,以及LIGHT(CD 258)与HVEM(CD 270)和LTBR(α-光毒素β受体)相互作用的假说进行了验证。
在具有不同严重程度哮喘的患者的肺中变应原诱导的炎症和重塑的特征;这些分子将在暴露于鼻病毒(一种与哮喘恶化相关的病原体)的患者的肺中进一步诱导;并且它们将在功能上与支气管上皮细胞和肺巨噬细胞,成纤维细胞,
和T细胞。目前哮喘患者的治疗选择有限。了解这些TNF/TNFR家族分子表达的时间和位置,以及它们相互作用产生的功能活动,可能会为急性和慢性哮喘的治疗干预带来新的和新的靶点。
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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Michael Croft其他文献
Michael Croft的其他文献
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{{ truncateString('Michael Croft', 18)}}的其他基金
A Treg cell-intrinsic CTLA4-PKC-eta signaling pathway mediating contact-dependent suppression of tumor immunity: A novel target for cancer immunotherapy
Treg 细胞固有的 CTLA4-PKC-eta 信号通路介导接触依赖性肿瘤免疫抑制:癌症免疫治疗的新靶点
- 批准号:
10531229 - 财政年份:2018
- 资助金额:
$ 45.55万 - 项目类别:
A Treg cell-intrinsic CTLA4-PKC-eta signaling pathway mediating contact-dependent suppression of tumor immunity: A novel target for cancer immunotherapy
Treg 细胞固有的 CTLA4-PKC-eta 信号通路介导接触依赖性肿瘤免疫抑制:癌症免疫治疗的新靶点
- 批准号:
10053328 - 财政年份:2018
- 资助金额:
$ 45.55万 - 项目类别:
A Treg cell-intrinsic CTLA4-PKC-eta signaling pathway mediating contact-dependent suppression of tumor immunity: A novel target for cancer immunotherapy
Treg 细胞固有的 CTLA4-PKC-eta 信号通路介导接触依赖性肿瘤免疫抑制:癌症免疫治疗的新靶点
- 批准号:
10310411 - 财政年份:2018
- 资助金额:
$ 45.55万 - 项目类别:
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