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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 对哮喘，特别是严重哮喘的发病机制仍然知之甚少。 我们实验室以前的工作表明，哮喘受试者气道的上皮细胞和成纤维细胞都可能参与疾病过程。 此外，向这些细胞中添加生长因子（转化生长因子β）和Th 2（过敏相关）细胞因子白介素13诱导可能重要的多种应答。 在对这些因素的反应中似乎存在遗传差异。 目前的研究将评估IL-13和TCF-β单独或联合对来自患有和不患有哮喘的人类受试者的肺上皮细胞和成纤维细胞的作用，其与这些反应相关的遗传背景是已知的。 我们将专门讨论这些因素对上皮细胞中粘液产生的影响，以及一种有效的化学物质，它吸引嗜酸性粒细胞进入成纤维细胞的气道（嗜酸性粒细胞趋化因子）。 然后，我们将研究导致这些反应的遗传和分子机制。 最后，这些通路中遗传异常的影响也将在一系列哮喘受试者和正常对照的临床和生理临床水平上得到解决。

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.