Yersinia enterocolitica YopT and Clostridium difficile toxin B induce expression of GILZ in epithelial cells.
Yersinia enterocolitica YopT and Clostridium difficile toxin B induce expression of GILZ in epithelial cells.
复制标题
DOI：
10.1371/journal.pone.0040730
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bohn E
中科院分区：
文献类型：
--
作者：
Köberle M;Göppel D;Grandl T;Gaentzsch P;Manncke B;Berchtold S;Müller S;Lüscher B;Asselin-Labat ML;Pallardy M;Sorg I;Langer S;Barth H;Zumbihl R;Autenrieth IB;Bohn E
糖皮质激素诱导的亮氨酸拉链（GILZ）已被证明是由不同的刺激，如糖皮质激素，IL-10或剥夺IL-2诱导细胞。GILZ具有抗炎特性，并可能参与细胞凋亡的信号调节。在此，我们证明了携带pYV质粒的野生型小肠结肠炎耶尔森氏菌上调上皮细胞中GILZ mRNA水平和蛋白表达。用不同的耶尔森氏菌突变株感染HeLa细胞显示，切割Rho GTP酶的膜结合形式的YopT的蛋白酶活性足以诱导GILZ表达。类似地，艰难梭菌毒素B（Rho GTP酶的另一种细菌抑制剂）诱导GILZ表达。YopT和毒素B均增加HeLa细胞中GILZ启动子的转录活性。GILZ表达不能与这些毒素对单个Rho GT3的失活联系起来。然而，RhoA和RhoB的强制表达降低了基础GILZ启动子活性。此外，MAPK激活证明是必要的深刻GILZ诱导毒素B。启动子研究和凝胶位移分析确定了上游刺激因子（USF）1和2与GILZ启动子中典型的c-Myc结合位点（E-box）的结合是其反式激活的关键步骤。此外，我们可以表明USF-1和USF-2对于基础以及毒素B诱导的GILZ表达是必需的。这些发现定义了细菌毒素介导的GILZ启动子反式激活的新方式，并将其与地塞米松或剥夺IL-2介导的方式区分开来。
Glucocorticoid induced-leucine zipper (GILZ) has been shown to be induced in cells by different stimuli such as glucocorticoids, IL-10 or deprivation of IL-2. GILZ has anti-inflammatory properties and may be involved in signalling modulating apoptosis. Herein we demonstrate that wildtype Yersinia enterocolitica which carry the pYV plasmid upregulated GILZ mRNA levels and protein expression in epithelial cells. Infection of HeLa cells with different Yersinia mutant strains revealed that the protease activity of YopT, which cleaves the membrane-bound form of Rho GTPases was sufficient to induce GILZ expression. Similarly, Clostridium difficile toxin B, another bacterial inhibitor of Rho GTPases induced GILZ expression. YopT and toxin B both increased transcriptional activity of the GILZ promoter in HeLa cells. GILZ expression could not be linked to the inactivation of an individual Rho GTPase by these toxins. However, forced expression of RhoA and RhoB decreased basal GILZ promoter activity. Furthermore, MAPK activation proved necessary for profound GILZ induction by toxin B. Promoter studies and gel shift analyses defined binding of upstream stimulatory factor (USF) 1 and 2 to a canonical c-Myc binding site (E-box) in the GILZ promoter as a crucial step of its trans-activation. In addition we could show that USF-1 and USF-2 are essential for basal as well as toxin B induced GILZ expression. These findings define a novel way of GILZ promoter trans-activation mediated by bacterial toxins and differentiate it from those mediated by dexamethasone or deprivation of IL-2.
登录
查看更多内容
影响因子：
5.8
作者：
Adkins, Irena;Koeberle, Martin;Autenrieth, Ingo B.
通讯作者：
Autenrieth, Ingo B.
影响因子：
11.4
作者：
FERREDAMARE, AR;POGNONEC, P;BURLEY, SK
通讯作者：
BURLEY, SK
影响因子：
15.9
作者：
Ayroldi, Emira;Zollo, Ornella;Riccardi, Carlo
通讯作者：
Riccardi, Carlo
影响因子：
14.2
作者：
Eddleston, Jane;Herschbach, Jack;Zuraw, Bruce L.
通讯作者：
Zuraw, Bruce L.
影响因子：
5.8
作者：
Ausiello, Clara Maria;Cerquetti, Marina;Mastrantonio, Paola
通讯作者：
Mastrantonio, Paola