Studies on emetic activity and mechanism of staphylococcal enterotoxin A

葡萄球菌肠毒素A的催吐活性及机制研究

• 批准号: 15590379
• 负责人: HU Dong-liang
• 金额: $ 2.24万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590379/
• 关键词: staphylococcal enterotoxin; emetic activity; calcium; intestinal cell; NOS; カルシウム; サイトカイン; iNos; eNOS

Staphylococcal enterotoxins (SEs) are exotoxic proteins produced by Staphylococcus aureus that cause staphylococcal food poisoning and toxic shock syndrome in humans and other species. However, the pathogenesis of SEs-mediated food poisoning, which causes diarrhea and vomiting within about 4-6 h of ingesting contaminated food, is not clearly understood.In this study, we constructed and expressed mutants of SEA and investigated emetic and superantigenic activity of these mutant SEAs. Furthermore, to clarify whether SEA can affect any changes of cellular signalling pathways in intestinal epithelial cells, we performed experiments to see if SEA can modulate the intracellular signaling pathway in intestinal epithelial cells. Our results demonstrated for the first time that staphylococcal enterotoxin A (SEA) induces an increase in intracellular calcium ([Ca^<2+>]i) in human intestinal epithelial cells and the [Ca^<2+>]i is released from intracellular stores. SEA-induced increase of [Ca^<2+>]i was clearly inhibited by treatment with a nitric oxide synthase (NOS) inhibitor, N^G-monomethyl-L-arginine. Intestinal epithelial cells express endothelial NOS in resting cell condition, and express inducible NOS after stimulating with tumor necrosis factor (TNF)-α. TNF-α-pretreated cells showed a significant increase in [Ca^<2+>]i that was also inhibited by the NOS inhibitor. These results suggest that SEA modulated [Ca^<2+>]i signal is dependent on NOS expression in human intestinal epithelial cells.

金黄色葡萄球菌肠毒素（Staphylococcal enterotoxins，SE）是由金黄色葡萄球菌（Staphylococcus aureus）产生的一种外毒蛋白，可引起人类和其他物种的葡萄球菌性食物中毒和中毒性休克综合征。然而，SEs介导的食物中毒的发病机制尚不清楚，在大约4-6小时内的ingredient污染的食物引起腹泻和呕吐。此外，为了阐明SEA是否可以影响肠上皮细胞中细胞信号通路的任何变化，我们进行了实验，看看SEA是否可以调节肠上皮细胞中的细胞内信号通路。我们的研究结果首次证实了葡萄球菌肠毒素A（SEA）可诱导人肠上皮细胞内钙（[Ca^2+]i）的增加，并使[Ca^2+]i从细胞内释放出来。用一氧化氮合酶（NOS）抑制剂N^G-单甲基-L-精氨酸处理可明显抑制SEA诱导的[Ca^2+]i升高。肠上皮细胞在静息状态下表达内皮型NOS，在肿瘤坏死因子（TNF-α）刺激后表达诱导型NOS。TNF-α预处理的细胞显示[Ca^<2+>]i显著增加，这也被NOS抑制剂抑制。这些结果表明SEA调节的[Ca^<2+>]i信号依赖于人肠上皮细胞中NOS的表达。

项目成果

Identification and characterization of a new staphylococcal enterotoxin-related putative toxin encoded by two kinds of plasmids

• DOI: 10.1128/iai.71.10.6088-6094.2003
• 发表时间: 2003-10-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Omoe, K;Hu, DL;Shinagawa, K
• 通讯作者: Shinagawa, K

Biological Properties of Staphylococcal Enterotoxin-Like Toxin Type R

• DOI: 10.1128/iai.72.6.3664-3667.2004
• 发表时间: 2004-06
• 期刊: Infection and Immunity
• 影响因子: 3.1
• 作者: K. Omoe;K. Imanishi;D. Hu;H. Kato;H. Takahashi-Omoe;A. Nakane;T. Uchiyama;K. Shinagawa

Vaccination with nontoxic mutant toxic shock syndrome toxin 1 protects against Staphylococcus aureus infection

• DOI: 10.1086/377308
• 发表时间: 2003-09-01
• 期刊: JOURNAL OF INFECTIOUS DISEASES
• 影响因子: 6.4
• 作者: Hu, DL;Omoe, K;Nakane, A
• 通讯作者: Nakane, A

Hu, D-L. et al.: "Vaccination with nontoxic mutant toxic shock syndrome toxin 1 protects against Staphylococcus aureus infection"The Journal of Infectious Diseases. 188・9. 743-752 (2003)

Hu, D-L. 等：“接种无毒突变型中毒性休克综合征毒素 1 可预防金黄色葡萄球菌感染”《传染病杂志》188・9 (2003)。

Immunization with glutathione S-transferase and mutant toxic shock syndrome toxin 1 fusion protein protects against Staphylococcus aureus infection

• DOI: 10.1016/j.femsim.2005.01.010
• 发表时间: 2005-07-01
• 期刊: FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY
• 作者: Cui, JC;Hu, DL;Nakane, A
• 通讯作者: Nakane, A