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J Biol Chem, Vol. 275, Issue 19, 14084-14094, May 12, 2000

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*

Lars EckmannDagger , Jennifer R. Smith, Michael P. Housley, Michael B. Dwinell, and Martin F. Kagnoff

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-2alpha ), kinases (TKT, Eck, HEK), transcription factors (interferon regulatory factor-1), and HLA class I were the most prominent. Furthermore, the transcription factor NF-kappa 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.

Dagger 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.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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