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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：
8330059
负责人：
Michael Croft
金额：
$ 45.09万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
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 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8330059
关键词：
Acute Allergens Allergic Asthma Automobile Driving Breathing Cell Differentiation process Cells Characteristics Chronic Clinical Collagen Complement Data Deposition Development Disease Epithelial Epithelial Cells Epithelium Event Exposure to Extracellular Matrix Proteins Family Family member Fibroblasts Fibronectins Fibrosis Goals Human Hyperplasia Immune Immune response Infection Infection prevention Infiltration Inflammation Inflammatory Instruction Knowledge Laminin Lead Leucocytic infiltrate Ligands Light Link Lung Lung Inflammation Lymphocyte Mediating Mesenchymal Metaplasia Modeling Molecular Mucous body substance Mus Pathogenesis Pathway interactions Patients Pattern recognition receptor Phase Predisposition Process Production Proteins Regulation Rhinovirus Role Sampling Satellite Viruses Severities Signal Transduction Smooth Muscle Smooth Muscle Actin Staining Method Source Specimen Stimulus Surface T-Lymphocyte TGFB1 gene TNFSF4 gene Tenascin Testing Th2 Cells Therapeutic Intervention Tumor Necrosis Factor Receptor Tumor Necrosis Factor-alpha Virus airborne allergen airway inflammation airway remodeling angiogenesis asthmatic patient bronchial epithelium cell type eosinophil high voltage electron microscopy human data lymphotoxin beta receptor macrophage mast cell member muscle form muscle hypertrophy novel pathogen receptor thought 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.

项目概述（见说明）：