IFN-γ, But Not Fas, Mediates Reduction of Allergen-Induced Mucous Cell Metaplasia by Inducing Apoptosis
IFN-γ, But Not Fas, Mediates Reduction of Allergen-Induced Mucous Cell Metaplasia by Inducing Apoptosis
复制标题
IFN-γ（而非 Fas）通过诱导细胞凋亡介导减少过敏原诱导的粘液细胞化生
DOI：
10.4049/jimmunol.168.9.4764
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Y. Tesfaigzi
中科院分区：
文献类型：
--
作者：
Zha O;M. J. Fischer;G. T. De Sanctis;M. Schuyler;Y. Tesfaigzi
由过敏原暴露诱导的炎症反应通过现有和增殖的上皮细胞分化成粘液储存细胞而引起粘液细胞化生（MCM）。气道上皮细胞具有多种机制来解决这些变化以形成正常的气道上皮细胞。在这份报告中，我们首先调查了粘液细胞化生的状态和MCM减少的机制，尽管持续暴露于过敏原。过敏原暴露5天后，广泛的MCM已开发，但减少过敏原挑战时，持续15天。在此暴露期间，支气管肺泡灌洗液中IL-13水平降低，IFN-γ水平升高。相反，IL-13水平降低，但IFN-γ在停止变应原暴露后MCM消退期间的任何时间点均未检测到。IFN-γ而非抗Fas的滴注导致MCM的加速消退，并且在暴露于过敏原15天的Stat 1缺陷小鼠中MCM未消退，证实IFN-γ对于在长期暴露于过敏原期间减少MCM至关重要。IFN-γ而非抗Fas诱导增殖的正常人支气管上皮细胞和哮喘受试者的人支气管上皮细胞的凋亡性细胞死亡。IFN-γ的凋亡作用是caspase依赖性的，并被IL-13抑制，表明哮喘患者的Th 2环境可能通过防止化生粘液细胞的细胞死亡来维持MCM。这些研究可能有助于理解导致气道慢性变化的缺陷，并设计新的治疗方法来逆转哮喘患者的MCM和气道阻塞。
Inflammatory responses induced by allergen exposure cause mucous cell metaplasia (MCM) by differentiation of existing and proliferating epithelial cells into mucus-storing cells. Airway epithelia have various mechanisms that resolve these changes to form normal airway epithelia. In this report, we first investigated the state of mucous cell metaplasia and the mechanisms by which MCM is reduced despite continued exposures to allergen. After 5 days of allergen exposure, extensive MCM had developed but was reduced when allergen challenge was continued for 15 days. During this exposure period, IL-13 levels decreased and IFN-γ levels increased in the bronchoalveolar lavage fluid. In contrast, IL-13 levels decreased but IFN-γ was not detected at any time point during the resolution of MCM following cessation of allergen exposure. Instillation of IFN-γ but not anti-Fas caused accelerated resolution of MCM and MCM was not resolved in Stat1-deficient mice exposed to allergen for 15 days, confirming that IFN-γ is crucial for reducing MCM during prolonged exposures to allergen. IFN-γ but not anti-Fas induced apoptotic cell death in proliferating normal human bronchial epithelial cells and in human bronchial epithelial cells from subjects with asthma. The apoptotic effect of IFN-γ was caspase dependent and was inhibited by IL-13, indicating that the Th2 milieu in asthmatics may maintain MCM by preventing cell death in metaplastic mucous cells. These studies could be useful in the understanding of deficiencies leading to chronicity in airway changes and designing novel therapies to reverse MCM and airway obstruction in asthmatics.
登录
查看更多内容
影响因子：
20.3
作者：
HUSS, R;HOY, CA;DEEG, HJ
通讯作者：
DEEG, HJ
影响因子：
15.9
作者：
Longphre, M;Li, D;Basbaum, C
通讯作者：
Basbaum, C
影响因子：
4.4
作者：
G. Lack;K. Bradley;Eckard Hamelmann;H. Renz;J. Loader;D. Leung;G. Larsen;E. Gelfand
通讯作者：
G. Lack;K. Bradley;Eckard Hamelmann;H. Renz;J. Loader;D. Leung;G. Larsen;E. Gelfand
Bcl-2 在 LPS 和过敏原诱导的布朗挪威大鼠气道上皮增生粘液细胞中。
DOI：
10.1152/ajplung.2000.279.6.l1210
发表时间：
2000
期刊：
American journal of physiology. Lung cellular and molecular physiology
影响因子：
--
作者：
Tesfaigzi,Y;Fischer,MJ;Martin,AJ;Seagrave,J
通讯作者：
Seagrave,J
粘膜 IFN-γ 基因转移抑制小鼠肺部过敏反应。
DOI：
--
发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Li,XM;Chopra,RK;Chou,TY;Schofield,BH;Wills-Karp,M;Huang,SK
通讯作者：
Huang,SK