期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 42, 期 2, 页码 140-148出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2008-0419OC
关键词
idiopathic pulmonary fibrosis; c-FLIP; lung; epithelium; myofibroblast
资金
- National Institutes of Health [HL068628, HL055549, HL67671]
Increased apoptosis of alveolar epithelial cells and impaired apoptosis of myofibroblasts have been linked to the pathogenesis of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). Fas, a death receptor of the TNF-receptor superfamily, has been implicated in apoptosis of both cell types, though the mechanisms are poorly understood. The goals of this study were: (1) to examine the localization of Fas-associated death-domain-like IL-1 beta-converting enzyme inhibitory protein (c-FLIP), an NF-kappa B-dependent regulator of Fas-signaling, in lung tissues from IPF/UIP patients and control subjects; and (2) to compare c-FLIP expression with epithelial cell and myofibroblast apoptosis, proliferation, and NF-kappa B activation. c-FLIP expression was restricted to airway epithelial cells in control lung tissues. In contrast, in patients with IPF/UIP, c-FLIP was also expressed by alveolar epithelial cells in areas of injury and fibrosis, but was absent from myofibroblasts in fibroblastic foci and from alveolar epithelial cells in uninvolved areas of lung tissue. Quantification of apoptosis and proliferation revealed an absence of apoptotic or proliferating cells in fibroblastic foci and low levels of apoptosis and proliferation by alveolar epithelial cells. Quantification of NF-kappa B expression and nuclear translocation revealed strong staining and translocation in alveolar epithelial cells and weak staining and minimal nuclear translocation in myofibroblasts. These findings suggest that: (1) c-FLIP expression is induced in the abnormal alveolar epithelium of patients with IPF/UIP, (2) the resistance of myofibroblasts to apoptosis in patients with JPF/UIP occurs independently of c-FLIP expression, and (3) increased NF-kappa B activation and c-FLIP expression by the alveolar epithelium may be linked.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据