Airway inflammation and remodeling in asthma. Lessons from interleukin 11 and interleukin 13 transgenic mice.
Airway inflammation and remodeling in asthma. Lessons from interleukin 11 and interleukin 13 transgenic mice.
复制标题
哮喘中的气道炎症和重塑。
DOI：
--
复制
发表时间：
2001
影响因子：
24.7
通讯作者：
Jack A. Elias
中科院分区：
文献类型：
--
作者：
Zhou Zhu;C. Lee;T. Zheng;G. Chupp;Jingming Wang;R. Homer;P. Noble;Q. Hamid;Jack A. Elias
非炎症性结构改变，不同地称为气道重塑，在哮喘气道中有很好的记录。然而，这些改变的发病机制、气道重塑在哮喘表型产生中的重要性以及气道重塑反应的自然史尚未得到充分的定义。由于过度的细胞因子产生是哮喘气道的一个特征，我们使用组成型和诱导型过表达转基因系统来研究白细胞介素11 （IL-11）和IL-13可能对气道重塑反应的贡献。这些研究表明，这两种细胞因子在小鼠气道中产生的反应具有与人类哮喘组织相似的特征。IL-11引起气道纤维化，并增强间质胶原、肌细胞和肌成纤维细胞的积累。IL-13引起粘膜化生，增强粘蛋白基因表达，增强组织透明质酸积累和上皮下纤维化。重要的是，IL-11最容易在严重气道重构的哮喘受试者的组织中检测到，这与IL-11转基因小鼠相似。此外，IL-11可抑制哮喘样炎症，同时刺激气道纤维化。这表明IL-11的细化在一定程度上是气道愈合的一种尝试。最后，描述了一种新的三重转基因系统，允许转基因表达以真正的“开/关”方式进行调节。该系统可能有助于确定转基因诱导的气道重塑反应的可逆性。
Noninflammatory structural alterations, variously referred to as airway remodeling, are well documented in the asthmatic airway. However, the pathogenesis of these alterations, the importance of airway remodeling in generating the asthma phenotype, and the natural history of airway remodeling responses have not been adequately defined. Because exaggerated cytokine production is a characteristic feature of the asthmatic airway, we used constitutive and inducible overexpression transgenic systems to investigate the contributions that interleukin 11 (IL-11) and IL-13 might make to airway remodeling responses. These studies demonstrated that both cytokines produce responses in the murine airway with features similar to those in human asthmatic tissues. IL-11 caused airway fibrosis with the enhanced accumulation of interstitial collagens, myocytes, and myofibroblasts. IL-13 caused mucous metaplasia, enhanced mucin gene expression, enhanced tissue hyaluronic acid accumulation, and subepithelial fibrosis. Importantly, IL-11 was detected most readily in tissues from asthmatic subjects with severe airway remodeling that was similar to that seen in the IL-11 transgenic mice. In addition, IL-11 was shown to inhibit asthma-like inflammation while stimulating airway fibrosis. This suggests that IL-11 elaboration is, in part, an attempt at airway healing. Last, a novel triple transgenic system is described that allows transgene expression to be regulated in a true "on/off" manner. This system may be useful in defining the reversibility of transgene-induced airway remodeling responses.
DOI：
--
发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Rochester,CL;Ackerman,SJ;Zheng,T;Elias,JA
通讯作者：
Elias,JA
组胺可增强人肺成纤维细胞细胞因子刺激的 IL-11 产生。
DOI：
--
发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zheng,T;Nathanson,MH;Elias,JA
通讯作者：
Elias,JA
DOI：
10.1152/ajplung.1997.273.3.l648
发表时间：
1997-09-01
影响因子：
4.9
作者：
Elias, JA;Wu, Y;Panettieri, R
通讯作者：
Panettieri, R