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B Is a Central Regulator of the Intestinal Epithelial Cell Innate Immune Response Induced by Infection with Enteroinvasive Bacteria1
Laboratory of Mucosal Immunology, Department of Medicine, University of California at San Diego, La Jolla, CA 92093
Human intestinal epithelial cells up-regulate the expression of an
inflammatory gene program in response to infection with a spectrum of
different strains of enteroinvasive bacteria. The conserved nature of
this program suggested that diverse signals, which are activated by
enteroinvasive bacteria, can be integrated into a common signaling
pathway that activates a set of proinflammatory genes in infected host
cells. Human intestinal epithelial cell lines, HT-29, Caco-2, and T84,
were infected with invasive bacteria that use different strategies to
induce their uptake and have different intracellular localizations
(i.e., Salmonella dublin, enteroinvasive
Escherichia coli, or Yersinia
enterocolitica). Infection with each of these bacteria resulted
in the activation of TNF receptor associated factors, two recently
described serine kinases, I
B kinase (IKK) 
and IKK
, and
increased NF-B DNA binding activity. This was paralleled by partial
degradation of IB and IB
in bacteria-infected Caco-2 cells.
Mutant proteins that act as superrepressors of IKK and IB
inhibited the up-regulated transcription and expression of downstream
targets genes of NF-B that are key components of the epithelial
inflammatory gene program (i.e., IL-8, growth-related oncogene-,
monocyte chemoattractant protein-1, TNF-, cyclooxygenase-2, nitric
oxide synthase-2, ICAM-1) activated by those enteroinvasive bacteria.
These studies position NF-B as a central regulator of the epithelial
cell innate immune response to infection with enteroinvasive
bacteria.
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L. Eckmann, J. R. Smith, M. P. Housley, M. B. Dwinell, and M. F. Kagnoff 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 J. Biol. Chem., May 5, 2000; 275(19): 14084 - 14094. [Abstract] [Full Text] [PDF]
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U. Bocker, A. Schottelius, J. M. Watson, L. Holt, L. L. Licato, D. A. Brenner, R. B. Sartor, and C. Jobin Cellular Differentiation Causes a Selective Down-regulation of Interleukin (IL)-1beta -mediated NF-kappa B Activation and IL-8 Gene Expression in Intestinal Epithelial Cells J. Biol. Chem., April 14, 2000; 275(16): 12207 - 12213. [Abstract] [Full Text] [PDF]
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D. F. McCole, L. Eckmann, F. Laurent, and M. F. Kagnoff Intestinal Epithelial Cell Apoptosis following Cryptosporidium parvum Infection Infect. Immun., March 1, 2000; 68(3): 1710 - 1713. [Abstract] [Full Text] [PDF]
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C. Jobin and R. B. Sartor The Ikappa B/NF-kappa B system: a key determinant of mucosal inflammation and protection Am J Physiol Cell Physiol, March 1, 2000; 278(3): C451 - C462. [Abstract] [Full Text] [PDF]
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 M. Zamanian-Daryoush, T. H. Mogensen, J. A. DiDonato, and B. R. G. Williams NF-kappa B Activation by Double-Stranded-RNA-Activated Protein Kinase (PKR) Is Mediated through NF-kappa B-Inducing Kinase and Ikappa B Kinase Mol. Cell. Biol., February 15, 2000; 20(4): 1278 - 1290. [Abstract] [Full Text]
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 B. S. Hall, W. Tam, R. Sen, and M. E. A. Pereira Cell-specific Activation of Nuclear Factor-kappa B by the Parasite Trypanosoma cruzi Promotes Resistance to Intracellular Infection Mol. Biol. Cell, January 1, 2000; 11(1): 153 - 160. [Abstract] [Full Text]
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D. A. O'Neil, E. M. Porter, D. Elewaut, G. M. Anderson, L. Eckmann, T. Ganz, and M. F. Kagnoff Expression and Regulation of the Human {beta}-Defensins hBD-1 and hBD-2 in Intestinal Epithelium J. Immunol., December 15, 1999; 163(12): 6718 - 6724. [Abstract] [Full Text] [PDF]
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O. Steele-Mortimer, L. A. Knodler, S. L. Marcus, M. P. Scheid, B. Goh, C. G. Pfeifer, V. Duronio, and B. B. Finlay Activation of Akt/Protein Kinase B in Epithelial Cells by the Salmonella typhimurium Effector SigD J. Biol. Chem., November 22, 2000; 275(48): 37718 - 37724. [Abstract] [Full Text] [PDF]
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