TGF-BETA2 AND IL-4RA PATHWAY INTERACTIONS IN ASTHMA

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The mechanisms driving asthma and particularly severe asthma remain poorly understood. Previous work from our laboratory has suggested that both epithelial cells and fibroblasts from the airways of asthmatic subjects are likely to contribute to the disease process. Further, the addition of a growth factor (transforming growth factor beta) and a Th2 (allergy related) cytokine, Interleukin 13, to these cells induces a variety of responses that are likely to be important. Genetic differences seem to exist in the responses to these factors. The current study will evaluate the effect of IL-13 and TCF-Beta alone or in combination, on lung epithelial cells and fibroblasts derived from human subjects, with and without asthma, whose genetic background related to these responses is known. We will specifically address the impact of these factors on mucus production in the epithelial cells and a potent chemical that attracts eosinophils to the airways (eotaxin) in fibroblasts. We will then look at the mechanisms, genetic and molecular, that lead to these responses. Finally, the impact of genetic abnormalities in these pathways will also be addressed at the clinical and physiologic clinical level in a range of asthma subjects and normal controls.