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Type: Journal article
Title: The 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 lines
Author: Wang, H.
Paton, J.
Herdman, B.
Rogers, T.
Beddoe, T.
Paton, A.
Citation: Infection and Immunity, 2013; 81(3):673-683
Publisher: Amer Soc Microbiology
Issue Date: 2013
ISSN: 0019-9567
Statement of
Hui Wang, James C. Paton, Brock P. Herdman, Trisha J. Rogers, Travis Beddoe, Adrienne W. Paton
Abstract: The 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.
Keywords: Intestinal 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, Drug
Rights: Copyright © 2013, American Society for Microbiology. All Rights Reserved.
RMID: 0020125809
DOI: 10.1128/IAI.01043-12
Grant ID:
Appears in Collections:Molecular and Biomedical Science publications

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