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dc.contributor.authorWang, H.en
dc.contributor.authorPaton, J.en
dc.contributor.authorHerdman, B.en
dc.contributor.authorRogers, T.en
dc.contributor.authorBeddoe, T.en
dc.contributor.authorPaton, A.en
dc.identifier.citationInfection and Immunity, 2013; 81(3):673-683en
dc.description.abstractThe principal function of bacterial AB5 toxin B subunits is to interact with glycan receptors on the surfaces of target cells and mediate the internalization of holotoxin. However, B subunit-receptor interactions also have the potential to impact cell signaling pathways and, in so doing, contribute to pathogenesis independently of the catalytic (toxic) A subunits. Various Salmonella enterica serovars, including Salmonella enterica serovar Typhi, encode an AB5 toxin (ArtAB), the A subunit of which is an ADP-ribosyltransferase related to the S1 subunit of pertussis toxin. However, although the A subunit is able to catalyze ADP-ribosylation of host G proteins, a cytotoxic phenotype has yet to be identified for the holotoxin. We therefore examined the capacity of the purified B subunit (ArtB) from S. Typhi to elicit cytokine, chemokine, and adhesion molecule responses in human macrophage (U937), colonic epithelial (HCT-8) cell, and brain microvascular endothelial cell (HBMEC) lines. Secretion of the chemokines monocyte chemotactic protein 1 (MCP-1) and interleukin 8 (IL-8) was increased in all three tested cell lines, with macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and granulocyte colony-stimulating factor (G-CSF) also significantly increased in U937 cells. ArtB also upregulated the cytokines tumor necrosis factor alpha (TNF-α) and IL-6 in HBMECs and HCT-8 cells, but not in U937 cells, while intercellular adhesion molecule 1 (ICAM-1) was upregulated in HCT-8 and U937 cells and vascular cell adhesion molecule 1 (VCAM-1) was upregulated in HBMECs. Thus, ArtB may contribute to pathogenesis independently of the A subunit by promoting and maintaining a strong inflammatory response at the site of infection.en
dc.description.statementofresponsibilityHui Wang, James C. Paton, Brock P. Herdman, Trisha J. Rogers, Travis Beddoe, Adrienne W. Patonen
dc.publisherAmer Soc Microbiologyen
dc.rightsCopyright © 2013, American Society for Microbiology. All Rights Reserved.en
dc.subjectIntestinal Mucosa; Brain; Cell Line; Macrophages; Endothelial Cells; Epithelial Cells; Humans; Salmonella typhi; Protein Subunits; Bacterial Toxins; Cytokines; Cell Adhesion; Gene Expression Regulation; Dose-Response Relationship, Drugen
dc.titleThe b subunit of an AB5 toxin produced by salmonella enterica serovar typhi up-regulates chemokines, cytokines, and adhesion molecules in human macrophage, colonic epithelial, and brain microvascular endothelial cell linesen
dc.typeJournal articleen
pubs.library.collectionMolecular and Biomedical Science publicationsen
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]en
Appears in Collections:Molecular and Biomedical Science publications

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