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J Biol Chem, Vol. 275, Issue 19, 14084-14094, May 12, 2000
From the Department of Medicine, University of California, San
Diego, La Jolla, California 92093
Many clinically important enteric pathogens
initiate disease by invading and passing through the intestinal
epithelium, a process accompanied by increased epithelial expression of
proinflammatory cytokines. To further define the role intestinal
epithelial cells play in initiating and modulating the host response to
infection with invasive bacteria, hybrid selection on high density
cDNA arrays was used to characterize the mRNA expression
profile of ~4,300 genes in human intestinal epithelial cells after
infection with the prototypic invasive bacteria,
Salmonella. Selected findings were further evaluated by
reverse transcription-polymerase chain reaction, Northern blot
analysis, and protein assays. Epithelial infection with
Salmonella significantly up-regulated mRNA expression of a relatively small fraction of all genes tested. Of these, several
cytokines (granulocyte colony-stimulating factor, inhibin A,
Epstein-Barr virus-induced gene 3, interleukin-8, macrophage inflammatory protein-2
Analysis by High Density cDNA Arrays of Altered Gene
Expression in Human Intestinal Epithelial Cells in Response to
Infection with the Invasive Enteric Bacteria
Salmonella*
,
), kinases (TKT, Eck, HEK), transcription factors (interferon regulatory factor-1), and HLA class I were the most
prominent. Furthermore, the transcription factor NF-
B is shown to be
important for inducible mRNA expression for a broad group of genes
tested. These findings expand the repertoire of known epithelial cell
responses to infection with an invasive enteric pathogen. The results
also show that evaluation of mRNA expression profiles by cDNA
array analysis is a powerful approach to characterizing and
understanding host-pathogen interactions.
*
This work was supported by National Institutes of Health
Grant DK35108 and a research grant from the Crohn's and Colitis
Foundation of America.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: University of
California, San Diego, Department of Medicine 0623D, 9500 Gilman Dr.,
La Jolla, CA 92093-0623. Tel.: 858-534-0683; Fax: 858-534-5691; E-mail:
leckmann@ucsd.edu.
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