Abstract
The Helicobacter pylori immunodominant protein, CagA, is associated with severe gastritis and carcinoma. Injection of CagA into gastric epithelial cells by type IV secretion leads to actin-cytoskeletal rearrangements and cell scattering. CagA has been reported to have no role in the induction of transcription factor NF-kappaB and IL-8, which are crucial determinants for chronic inflammation. Here, we provide several lines of evidence showing that CagA is able to induce IL-8 in a time- and strain-dependent manner. We also show that by exchanging specific cagA genes, high IL-8-inducing H. pylori strains could be converted into low inducing strains and vice versa. Our results suggest that IL-8 release induced by CagA occurs via a Ras-->Raf-->Mek-->Erk-->NF-kappaB signaling pathway in a Shp-2- and c-Met-independent manner. Thus, CagA is a multifunctional protein capable of effecting both actin remodeling and potentiation of chemokine release.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / chemistry
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Active Transport, Cell Nucleus
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Antigens, Bacterial / chemistry
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Antigens, Bacterial / metabolism*
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Bacterial Adhesion
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Bacterial Proteins / chemistry
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Bacterial Proteins / metabolism*
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Cell Line, Tumor
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Cloning, Molecular
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Cytoskeleton / metabolism
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Enzyme Inhibitors / pharmacology
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Enzyme-Linked Immunosorbent Assay
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Epithelial Cells / microbiology
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Gastric Mucosa / metabolism
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Genetic Complementation Test
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Genomic Islands
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Green Fluorescent Proteins / metabolism
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Helicobacter pylori / metabolism*
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Humans
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Immunoblotting
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Inflammation
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Interleukin-8 / metabolism
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Intracellular Signaling Peptides and Proteins / metabolism
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Microscopy, Fluorescence
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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NF-kappa B / metabolism*
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Protein Binding
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Protein Transport
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases / metabolism
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Proto-Oncogene Proteins c-met / metabolism
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Sequence Analysis, DNA
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Stomach Neoplasms / microbiology
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Time Factors
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Transcription, Genetic
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Transfection
Substances
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Actins
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Antigens, Bacterial
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Bacterial Proteins
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Enzyme Inhibitors
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Interleukin-8
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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cagA protein, Helicobacter pylori
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Green Fluorescent Proteins
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Proto-Oncogene Proteins c-met
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PTPN11 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatases
Associated data
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GENBANK/DQ011619
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GENBANK/DQ011620