Group A Streptococcus Induces Apoptosis in Human Epithelial Cells
Group A Streptococcus Induces Apoptosis in Human Epithelial Cells
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A 族链球菌诱导人上皮细胞凋亡
DOI：
10.1128/iai.67.9.4334-4339.1999
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发表时间：
1999
影响因子：
3.1
通讯作者：
J. Wu
中科院分区：
文献类型：
--
作者：
P. Tsai;Yee‐Shin Lin;C. Kuo;H. Lei;J. Wu
摘要 A 族链球菌 (GAS) 被上皮细胞内化可能在引起侵袭性疾病中发挥作用。本研究的目的是检查 GAS 感染的上皮细胞的命运。 GAS具有侵入A-549和HEp-2细胞的能力。 A-549 和 HEp-2 细胞均被 GAS 感染杀死。 GAS 介导的上皮细胞死亡至少部分是通过细胞凋亡实现的，如细胞形态的变化、DNA 片段梯和亚二倍体细胞的碘化丙啶染色所示。 GAS感染20小时后，总共20%的A-549细胞和11%至13%的HEp-2细胞发生凋亡，而这些细胞中只有1%至2%表现出自发性凋亡。我们进一步检测了链球菌热原性外毒素 B (SPE B)（一种由 GAS 产生的半胱氨酸蛋白酶）是否参与上皮细胞的凋亡。 speB 同基因突变体诱导细胞死亡的能力比野生型菌株低。当A-549细胞与突变株和SPE B共培养2小时时，尽管胞内细菌数量增加到野生型菌株的水平，但凋亡细胞的百分比没有增加。此外，细胞松弛素 D 处理可阻断细胞凋亡，从而干扰细胞骨架功能。 Caspase 抑制剂 Z-VAD.FMK、Ac-YVAD.CMK 和 Ac-DEVD.FMK 抑制 GAS 诱导的细胞凋亡。这些结果首次证明GAS诱导上皮细胞凋亡，并且内化是细胞凋亡所必需的。 Caspase途径参与GAS诱导的细胞凋亡，细胞中SPE B的表达增强细胞凋亡。
ABSTRACT Internalization of group A streptococcus (GAS) by epithelial cells may have a role in causing invasive diseases. The purpose of this study was to examine the fate of GAS-infected epithelial cells. GAS has the ability to invade A-549 and HEp-2 cells. Both A-549 and HEp-2 cells were killed by infection with GAS. Epithelial cell death mediated by GAS was at least in part through apoptosis, as shown by changes in cellular morphology, DNA fragmentation laddering, and propidium iodide staining for hypodiploid cells. A total of 20% of A-549 cells and 11 to 13% of HEp-2 cells underwent apoptosis after 20 h of GAS infection, whereas only 1 to 2% of these cells exhibited spontaneous apoptosis. We further examined whether streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease produced by GAS, was involved in the apoptosis of epithelial cells. The speB isogenic mutants had less ability to induce cell death than wild-type strains. When A-549 cells were cocultured with the mutant and SPE B for 2 h, the percentage of apoptotic cells did not increase although the number of intracellular bacteria increased to the level of wild-type strains. In addition, apoptosis was blocked by cytochalasin D treatment, which interfered with cytoskeleton function. The caspase inhibitors Z-VAD.FMK, Ac-YVAD.CMK, and Ac-DEVD.FMK inhibited GAS-induced apoptosis. These results demonstrate for the first time that GAS induces apoptosis of epithelial cells and internalization is required for apoptosis. The caspase pathway is involved in GAS-induced apoptosis, and the expression of SPE B in the cells enhances apoptosis.
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DOI：
10.1073/pnas.90.16.7676
发表时间：
1993-08-15
影响因子：
11.1
作者：
KAPUR, V;MAJESKY, MW;MUSSER, JM
通讯作者：
MUSSER, JM
DOI：
10.1073/pnas.91.25.12115
发表时间：
1994-12-06
影响因子：
11.1
作者：
LAPENTA, D;RUBENS, C;CLEARY, PP
通讯作者：
CLEARY, PP
具有蛋白水解活性的链球菌热原性外毒素 B 可裂解单核细胞尿激酶受体，并从细胞表面释放受体的活性片段。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Wolf,BB;Gibson,CA;Kapur,V;Hussaini,IM;Musser,JM;Gonias,SL
通讯作者：
Gonias,SL
严重侵袭性 A 组链球菌疾病：临床描述和发病机制。
DOI：
10.1016/s0022-2143(96)90161-4
发表时间：
1996
期刊：
The Journal of laboratory and clinical medicine.
影响因子：
--
作者：
Schlievert,PM;Assimacopoulos,AP;Cleary,PP
通讯作者：
Cleary,PP
影响因子：
15.9
作者：
A. Zychlinsky;P. Sansonetti
通讯作者：
A. Zychlinsky;P. Sansonetti