霍乱弧菌溶细胞素促进肥大细胞（辅助性T细胞2）细胞因子的产生。
The Vibrio cholerae cytolysin promotes activation of mast cell (T helper 2) cytokine production.
作者信息
Arcidiacono Diletta, Odom Sandra, Frossi Barbara, Rivera Juan, Paccani Silvia R, Baldari Cosima T, Pucillo Carlo, Montecucco Cesare, de Bernard Marina
机构信息
Department of Biomedical Sciences, University of Padua, Via G. Colombo 3, 35121 Padua, Italy.
出版信息
Cell Microbiol. 2008 Apr;10(4):899-907. doi: 10.1111/j.1462-5822.2007.01092.x. Epub 2007 Nov 15.
Abstract
Many strains of Vibrio cholerae produce a cytolysin (VCC) that forms oligomeric transmembrane pores responsible for vacuolization of several cell types in culture. Here we suggest that VCC could contribute to the T helper 2 (Th2) response seen in the natural infection; acting through TLR2, VCC enhances mast cells secretion of IL-4, IL-6 and TNF-alpha by 330-, 290- and 550-fold respectively. Moreover, VCC-induced cytokine production is dependent on increased cytosolic Ca(2+) and on the presence of the Src family kinases Lyn and Fyn, known to be required for FcepsilonRI-dependent activation of mast cells. These findings strongly suggest that VCC has a pro-inflammatory activity promoting a Th2-type immune profile.
摘要
许多霍乱弧菌菌株会产生一种细胞溶素（VCC），它能形成寡聚跨膜孔，导致培养中的多种细胞类型出现空泡化。在此我们提出，VCC可能促成了自然感染中所见的辅助性T细胞2（Th2）反应；通过Toll样受体2（TLR2）发挥作用，VCC分别使肥大细胞分泌白细胞介素-4（IL-4）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）增加330倍、290倍和550倍。此外，VCC诱导的细胞因子产生依赖于胞质钙离子（Ca²⁺）的增加以及Src家族激酶Lyn和Fyn的存在，已知这两种激酶是FcεRI依赖性肥大细胞激活所必需的。这些发现有力地表明，VCC具有促进Th2型免疫特征的促炎活性。
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本文引用的文献
1
Activation of Ca2+-dependent signaling by TLR2.Toll样受体2（TLR2）介导的Ca2+依赖性信号激活
J Immunol. 2006 Jul 15;177(2):1330-7. doi: 10.4049/jimmunol.177.2.1330.
2
Src kinase Lyn is crucial for Pseudomonas aeruginosa internalization into lung cells.Src激酶Lyn对铜绿假单胞菌内化进入肺细胞至关重要。
Eur J Immunol. 2006 Jul;36(7):1739-52. doi: 10.1002/eji.200635973.
3
Molecular regulation of mast cell activation.肥大细胞激活的分子调控
J Allergy Clin Immunol. 2006 Jun;117(6):1214-25; quiz 1226. doi: 10.1016/j.jaci.2006.04.015.
4
The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses.幽门螺杆菌的中性粒细胞激活蛋白促进Th1免疫反应。
J Clin Invest. 2006 Apr;116(4):1092-101. doi: 10.1172/JCI27177. Epub 2006 Mar 16.
5
Increased expression of genes linked to FcepsilonRI Signaling and to cytokine and chemokine production in Lyn-deficient mast cells.在 Lyn 缺陷型肥大细胞中，与 FcεRI 信号传导以及细胞因子和趋化因子产生相关的基因表达增加。
J Immunol. 2005 Dec 15;175(12):7880-8. doi: 10.4049/jimmunol.175.12.7880.
6
A molecular model of the Vibrio cholerae cytolysin transmembrane pore.霍乱弧菌溶细胞素跨膜孔的分子模型。
Toxicon. 2006 Jan;47(1):35-40. doi: 10.1016/j.toxicon.2005.09.007. Epub 2005 Dec 5.
7
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J Biol Chem. 2006 Feb 3;281(5):2515-25. doi: 10.1074/jbc.M508931200. Epub 2005 Nov 29.
8
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J Immunol. 2005 Dec 1;175(11):7602-10. doi: 10.4049/jimmunol.175.11.7602.
9
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Cell Microbiol. 2005 Feb;7(2):191-8. doi: 10.1111/j.1462-5822.2004.00446.x.
10
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Immunol Rev. 2004 Dec;202:203-22. doi: 10.1111/j.0105-2896.2004.00209.x.
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