Vibrio vulnificus-induced Cell Death of Human Mononuclear Cells Requires ROS-dependent Activation of p38 and ERK 1/2 MAPKs
Vibrio vulnificus-induced Cell Death of Human Mononuclear Cells Requires ROS-dependent Activation of p38 and ERK 1/2 MAPKs
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DOI：
10.1080/08820130802500583
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发表时间：
2009-01-01
影响因子：
2.8
通讯作者：
Park, Soon-Jung
中科院分区：
文献类型：
--
作者：
Kim, Woo Hyang;Goo, Sung Young;Park, Soon-Jung
创伤弧菌是一种革兰氏阴性细菌，在宿主组织中迅速繁殖并引起广泛的组织损伤。人外周血单核细胞（PBMC）显示出容易通过暴露于活的创伤弧菌而被杀死。创伤弧菌诱导PBMC产生细胞内活性氧（ROS）和一氧化氮（NO）。用氯化二苯碘铵（DPI）预处理PBMC可消除暴露于创伤弧菌后ROS的产生，并降低细菌导致细胞死亡的能力。与此相反，这些细胞与诱导型一氧化氮合酶（iNOS）抑制剂的预处理阻断V. vunificus诱导的NO的产生，但没有显着改变V. vulnificus细胞死亡。创伤弧菌还触发PBMC中的促分裂原活化蛋白激酶（MAPK）（包括p38和ERK 1/2）的磷酸化。通过选择性抑制剂灭活这些MAPKs导致ROS产生和创伤弧菌诱导的细胞死亡减少。进一步显示，ROS生成抑制剂（DPI）阻断创伤弧菌诱导的p38和ERK 1/2 MAPK磷酸化。本研究表明创伤弧菌通过ROS依赖性激活p38 MAPK和ERK 1/2 MAPK诱导PBMC死亡。
Vibrio vulnificus is a Gram-negative bacterium that multiplies rapidly in host tissue and causes extensive tissue damage. Human peripheral blood mononuclear cells (PBMC) were shown to be readily killed by exposure to live V. vulnificus. V. vulnificus induced production of intracellular reactive oxygen species (ROS) and nitric oxide (NO) in PBMC. Pretreatment of PBMC with diphenyleneiodonium chloride (DPI) abolished ROS generation upon exposure to V. vulnificus and decreased the bacterial ability to cause cell death. In contrast, pretreatment of these cells with inhibitors of inducible nitric oxide synthase (iNOS) blocked V. vunificus-induced NO production, but did not significantly alter cell death by V. vulnificus. V. vulnificus also triggered phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 and ERK1/2 in PBMC. Inactivation of these MAPKs by selective inhibitors caused a reduction both in ROS generation and cell death induced by V. vulnificus. It was further shown that an inhibitor of ROS generation (DPI) blocked V. vulnificus-induced phosphorylation of p38 and ERK1/2 MAPK. This study demonstrates that V. vulnificus induces death of PBMC via ROS-dependent activation of p38 MAPK and ERK1/2 MAPK.