Anti-apoptotic effects of SERPIN B3 and B4 via STAT6 activation in macrophages after infection with Toxoplasma gondii.
Anti-apoptotic effects of SERPIN B3 and B4 via STAT6 activation in macrophages after infection with Toxoplasma gondii.
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弓形虫感染后巨噬细胞中 SERPIN B3 和 B4 通过 STAT6 激活的抗凋亡作用。
DOI：
10.3347/kjp.2012.50.1.1
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Nam HW
中科院分区：
文献类型：
--
作者：
Song KJ;Ahn HJ;Nam HW
弓形虫可穿透各种有核真核细胞，但对宿主细胞的调节作用不同，使其在细胞内存活。在之前的研究中，我们发现丝氨酸蛋白酶抑制剂B3和B4(SERPIN B3/B4，因为它们的同源性很高)可以通过激活STAT6在THP-1来源的巨噬细胞中显著诱导。为探讨SERPIN B3/B4对弓形虫感染THP-1细胞凋亡的影响，我们设计并检测了星状孢子素诱导THP-1细胞凋亡过程中SERPIN B3或B4的各种小干扰(si-)RNA。THP-1细胞感染弓形虫后，SERPIN B3/B4被SERPIN B3/B4基因敲除后，THP-1细胞的抗凋亡特性消失。这种抗凋亡作用在SERPIN B3/B4过表达的HeLa细胞中得到证实。我们还研究了抑制STAT6是否影响SERPIN B3/B4的功能，反之亦然。抑制SERPIN B3/B4不影响STAT6的表达，但STAT6si-RNA可抑制SERPIN B3/B4的表达，证实SERPIN B3/B4是在STAT6激活的控制下诱导的。这些结果表明，弓形虫通过激活STAT6来诱导SERPIN B3/B4的表达，从而抑制感染的THP-1细胞的凋亡，从而延长细胞内寄生虫的生存时间。
Toxoplasma gondii penetrates all kinds of nucleated eukaryotic cells but modulates host cells differently for its intracellular survival. In a previous study, we found out that serine protease inhibitors B3 and B4 (SERPIN B3/B4 because of their very high homology) were significantly induced in THP-1-derived macrophages infected with T. gondii through activation of STAT6. In this study, to evaluate the effects of the induced SERPIN B3/B4 on the apoptosis of T. gondii-infected THP-1 cells, we designed and tested various small interfering (si-) RNAs of SERPIN B3 or B4 in staurosporine-induced apoptosis of THP-1 cells. Anti-apoptotic characteristics of THP-1 cells after infection with T. gondii disappeared when SERPIN B3/B4 were knock-downed with gene specific si-RNAs transfected into THP-1 cells as detected by the cleaved caspase 3, poly-ADP ribose polymerase and DNA fragmentation. This anti-apoptotic effect was confirmed in SERPIN B3/B4 overexpressed HeLa cells. We also investigated whether inhibition of STAT6 affects the function of SERPIN B3/B4, and vice versa. Inhibition of SERPIN B3/B4 did not influence STAT6 expression but SERPIN B3/B4 expression was inhibited by STAT6 si-RNA transfection, which confirmed that SERPIN B3/B4 was induced under the control of STAT6 activation. These results suggest that T. gondii induces SERPIN B3/B4 expression via STAT6 activation to inhibit the apoptosis of infected THP-1 cells for longer survival of the intracellular parasites themselves.
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影响因子：
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