Fas/Fas ligand interactions are involved in ultraviolet-B-induced human lymphocyte apoptosis.

Fas/Fas ligand interactions are involved in ultraviolet-B-induced human lymphocyte apoptosis.
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DOI:
10.4049/jimmunol.161.1.241
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发表时间:
1998-07
影响因子:
4.4
通讯作者:
Roberto Caricchio;E. Reap;Philip L. Cohen
Roberto Caricchio;E. Reap;Philip L. Cohen
中科院分区:
医学2区
文献类型:
--
作者:
Roberto Caricchio;E. Reap;Philip L. Cohen

文献摘要

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我们想知道是否已知的细胞凋亡发生后,UV-B辐射可能涉及Fas/Fas配体(FasL)信号通路。我们暴露于PBLs从正常人,也Jurkat(E6-1)和U937细胞系,以分级剂量的UV-B照射,并观察到一个提示和显着增加Fas表达的剂量低至0.5毫焦耳/厘米2。Fas表达增加并不需要新的蛋白质合成,因为环己酰亚胺处理的细胞也表现出增加Fas后UV-B。UV-B照射的细胞在锌的存在下培养的细胞凋亡的抑制一致的Fas+细胞的显着增加,显然表明Fas-轴承细胞不能进行凋亡的积累。经UV-B照射后,E6-1淋巴细胞系Fas配体表达增加,并释放可溶性FasL。UV-B诱导的细胞凋亡可被FasL抗体部分阻断,FasL抗性的E6-1细胞株经UV-B照射后凋亡率降低,提示Fas表达的增加在UV-B诱导的细胞凋亡中起一定作用。UV诱导的Fas表达可用于靶向应激损伤的细胞,以通过携带FasL的细胞或通过细胞自身响应于刺激产生的FasL去除,并且可代表Fas/FasL途径在促进细胞凋亡和消除不期望的或有害的细胞中的一般功能。
We wondered whether the apoptosis known to occur after UV-B irradiation might involve the Fas/Fas ligand (FasL) signaling pathway. We exposed PBLs from normal individuals, and also the Jurkat (E6-1) and U937 cell lines, to graded doses of UV-B irradiation and observed a prompt and marked increase in Fas expression at doses as low as 0.5 mJ/cm2. Increased Fas expression did not require new protein synthesis, since cycloheximide-treated cells also showed an increase in Fas after UV-B. UV-B-irradiated cells cultured in the presence of zinc showed inhibition of apoptosis coincident with a marked increase in Fas+ cells, apparently indicating the accumulation of Fas-bearing cells unable to undergo apoptosis. After UV-B irradiation, PBLs showed increased expression of Fas ligand; the E6-1 lymphocytic cell line also released soluble FasL. UV-B induced apoptosis could be partially blocked by neutralizing FasL Abs, and a FasL-resistant variant of E6-1 cell line showed reduced apoptosis after UV-B irradiation, implying that the increase in Fas expression signified a role for Fas in UV-induced apoptosis. UV-induced Fas expression may serve to target stress-injured cells for removal by FasL-bearing cells or by FasL produced by the cells themselves in response to the stimuli, and may represent a general function of the Fas/FasL pathway in facilitating the apoptosis and elimination of undesirable or harmful cells.