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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism
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Cell Line
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Cells, Cultured
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Cytokines / genetics
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Cytokines / metabolism*
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Humans
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Interleukin-4 / genetics
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Interleukin-4 / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Mast Cells / cytology
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Mast Cells / drug effects*
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Mast Cells / metabolism
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Mice
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Mice, Knockout
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Perforin / genetics
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Perforin / metabolism
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Perforin / pharmacology*
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Proto-Oncogene Proteins c-fyn / genetics
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Proto-Oncogene Proteins c-fyn / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Toll-Like Receptor 2 / genetics
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Toll-Like Receptor 2 / metabolism
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Vibrio cholerae / metabolism*
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src-Family Kinases / genetics
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src-Family Kinases / metabolism
Substances
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Cytokines
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Interleukin-6
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RNA, Messenger
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Tlr2 protein, mouse
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Toll-Like Receptor 2
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Tumor Necrosis Factor-alpha
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Perforin
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Interleukin-4
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Fyn protein, mouse
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Proto-Oncogene Proteins c-fyn
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lyn protein-tyrosine kinase
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src-Family Kinases
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Calcium