Vibrio vulnificus-induced cell death of human mononuclear cells requires ROS-dependent activation of p38 and ERK 1/2 MAPKs.
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.
Kim
Woo Hyang
WH
Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Goo
Sung Young
SY
Lee
Kyu-Ho
KH
Park
Soon-Jung
SJ
D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000276:immunology / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D014735:Vibrio Infections / Q000201:enzymology / Q000276:immunology*; D041261:Vibrio vulnificus / Q000276:immunology* / Q000472:pathogenicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*
D009861:Onium Compounds; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C007517:diphenyleneiodonium; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases