Abstract
Helicobacter pylori (Hp) vacuolating cytotoxin VacA induces cellular vacuolation in epithelial cells. We found that VacA could efficiently block proliferation of T cells by inducing a G1/S cell cycle arrest. It interfered with the T cell receptor/interleukin-2 (IL-2) signaling pathway at the level of the Ca2+-calmodulin-dependent phosphatase calcineurin. Nuclear translocation of nuclear factor of activated T cells (NFAT), a transcription factor acting as a global regulator of immune response genes, was abrogated, resulting in down-regulation of IL-2 transcription. VacA partially mimicked the activity of the immunosuppressive drug FK506 by possibly inducing a local immune suppression, explaining the extraordinary chronicity of Hp infections.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Bacterial Proteins / pharmacology
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Bacterial Proteins / physiology*
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Bacterial Toxins / pharmacology
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Calcineurin / metabolism
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Calcineurin Inhibitors
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Cyclins / metabolism
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Cytotoxins / pharmacology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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G1 Phase
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Gene Expression Regulation
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HeLa Cells
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Helicobacter pylori / genetics
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Helicobacter pylori / pathogenicity*
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Humans
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Jurkat Cells
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Lymphocyte Activation*
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NFATC Transcription Factors
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Nuclear Proteins*
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Oligonucleotide Array Sequence Analysis
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S Phase
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Signal Transduction
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T-Lymphocytes / immunology*
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T-Lymphocytes / microbiology*
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T-Lymphocytes / physiology
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Tacrolimus / pharmacology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic
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Transfection
Substances
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Bacterial Proteins
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Bacterial Toxins
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Calcineurin Inhibitors
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Cyclins
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Cytotoxins
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DNA-Binding Proteins
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Interleukin-2
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NFATC Transcription Factors
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Nuclear Proteins
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Transcription Factors
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VacA protein, Helicobacter pylori
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Calcineurin
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Tacrolimus