Induction of salivary gland epithelial cell injury in sjogren's syndrome:: In vitro assessment of T cell-derived cytokines and fas protein expression
Induction of salivary gland epithelial cell injury in sjogren's syndrome:: In vitro assessment of T cell-derived cytokines and fas protein expression
复制标题
DOI：
10.1006/jaut.2001.0524
复制
发表时间：
2001-09-01
影响因子：
12.8
通讯作者：
Manoussakis, MN
中科院分区：
文献类型：
--
作者：
Abu-Helu, RF;Dimitriou, ID;Manoussakis, MN
干燥综合征（SS）是一种以T细胞浸润、唾液腺上皮细胞（SGEC）凋亡和Fas、FasL高表达为特征的外分泌病。为了解决T细胞衍生的细胞因子和Fas凋亡途径在SS腺体病变中的参与，我们利用从SS患者和对照建立的非肿瘤性SGEC系。可能证明其内在激活，细胞系来源于SS患者显示显着较高的组成型Fas和FasL比对照组。Fas和FasL的表面共表达与自发性杀兄弟性凋亡无关。SGEC对抗Fas介导的凋亡具有抗性（可能是由于抗凋亡蛋白cFLIP和Bcl-2的组成性表达），但在蛋白质或RNA合成抑制后变得敏感。IFN-γ和TNF-α能够上调表面Fas和FasL，而IL-1 β下调表面FasL。IFN-γ（而不是其他几种细胞因子）以密切和时间依赖性的方式降低SGEC的存活率，并直接或通过失巢诱导Fas/FasL介导的细胞凋亡。地塞米松可抑制IFN-γ上调SGEC Fas和FasL的表达，抑制抗Fas单抗或IFN-γ诱导SGEC凋亡和脱离。我们的研究结果表明IFN-γ通过诱导Fas介导的细胞凋亡和失巢症对SS患者唾液腺上皮细胞的损伤作用。(C)北京：科学出版社.
Sjogren's syndrome (SS) is an exocrinopathy characterized by T cell infiltrates, salivary gland epithelial cell (SGEC) apoptosis and high Fas and FasL expression. To address the participation of T cell-derived cytokines and of Fas apoptotic pathway in SS glandular lesions, we utilized non-neoplastic SGEC lines established from SS patients and controls. Possibly attesting to their intrinsic activation, cell lines derived from SS patients displayed significantly higher constitutive Fas and FasL than controls. Surface co-expression of Fas and FasL was not associated with spontaneous fratricide apoptosis. SGEC were resistant to anti-Fas-mediated apoptosis (possibly owing to the constitutive expression of anti-apoptotic proteins cFLIP and Bcl-2), but became sensitive after protein or RNA synthesis inhibition. IFN-gamma and TNF-alpha were able to upregulate surface Fas and FasL, whereas IL-1 beta downregulated surface FasL. IFN-gamma (but not several other cytokines) reduced the survival of SGEC in a close- and time-dependent manner and induced Fas/FasL-mediated apoptosis, directly and via anoikia. Dexamethasone inhibited the upregulation of Fas and FasL by IFN-gamma and the induction of SGEC apoptosis and detachment by anti-Fas mAb or IFN-gamma. Our findings indicate the injurious role of IFN-gamma for the salivary epithelia of SS patients through the induction of Fas-mediated apoptosis and anoikia. (C) 2001 Academic Press.