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https://hdl.handle.net/2440/3020
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Type: | Journal article |
Title: | Enhanced CXC chemokine responses of human colonic epithelial cells to locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli |
Author: | Rogers, T. Paton, A. McColl, S. Paton, J. |
Citation: | Infection and Immunity, 2003; 71(10):5623-5632 |
Publisher: | Amer Soc Microbiology |
Issue Date: | 2003 |
ISSN: | 0019-9567 1098-5522 |
Statement of Responsibility: | Trisha J. Rogers, Adrienne W. Paton, Shaun R. McColl, and James C. Paton |
Abstract: | There is increasing evidence that by facilitating translocation of Shiga toxin (Stx) across the intestinal epithelium and by transporting bound toxin to remote sites such as the renal endothelium, polymorphonuclear leukocytes (PMNs) play a key role in the pathogenesis of Shiga-toxigenic Escherichia coli (STEC) disease. Plasma levels of PMN-attracting CXC chemokines such as interleukin-8 (IL-8) also appear to correlate in humans with the severity of disease. Thus, the capacity of STEC strains to elicit CXC chemokine responses in intestinal epithelial cells may be a crucial step in pathogenesis. Accordingly, we attempted to determine which STEC factors are responsible for CXC chemokine induction in human colonic epithelial cells. Infection of Hct-8 cells with locus for enterocyte effacement (LEE)-negative STEC strains isolated from patients with severe STEC disease resulted in up-regulation of IL-8, macrophage inflammatory protein 2 (MIP-2), MIP-2ß, and ENA-78 mRNA significantly higher and earlier than that elicited by several LEE-positive STEC strains, including the O157:H7 strain EDL933. Similarly, levels of IL-8 protein in LEE-negative STEC-infected Hct-8 culture supernatants were significantly higher than in LEE-positive STEC-infected culture supernatants. The difference in responses could not be attributed to the expression or nonexpression of LEE genes, the presence or absence of an STEC megaplasmid, or differences in O serogroups or in the type or amount of Stx produced. Interestingly, however, several of the LEE-negative STEC strains eliciting the strongest chemokine responses belonged to flagellar serotype H21. Incubation of Hct-8 cells with isolated H21 flagellin elicited IL-8 and MIP-2 responses similar to those seen in the presence of the most potent LEE-negative STEC strains. Deletion of the fliC gene, but not the stx2 gene, largely abolished the capacity of O113:H21 LEE-negative STEC strain 98NK2 to elicit IL-8 and MIP-2 responses in Hct-8 cells. Taken together, these data suggest that although Stx is capable of inducing CXC chemokine responses, the elevated responses seen in cells infected with certain STEC strains are largely attributable to the production of flagellin. |
Keywords: | Colon Cell Line Epithelial Cells Humans Escherichia coli Escherichia coli Infections Gastroenteritis Escherichia coli Proteins Flagellin Phosphoproteins DNA RNA, Messenger Chemokines, CXC Interleukin-8 Virulence Up-Regulation Base Sequence Mutation Genes, Bacterial Shiga Toxin 2 |
Description: | Copyright © 2003, American Society for Microbiology. All Rights Reserved. |
DOI: | 10.1128/IAI.71.10.5623-5632.2003 |
Published version: | http://iai.asm.org/cgi/content/abstract/71/10/5623 |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
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