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https://hdl.handle.net/2440/79562
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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 1098-5522 |
Editor: | Pirofski, L. |
Statement of Responsibility: | 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. |
DOI: | 10.1128/IAI.01043-12 |
Grant ID: | http://purl.org/au-research/grants/arc/DP1095420 http://purl.org/au-research/grants/arc/DP120103178 http://purl.org/au-research/grants/arc/DP1095420 |
Published version: | http://dx.doi.org/10.1128/iai.01043-12 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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