Enteropathogenic Escherichia coli Outer Membrane Proteins Induce iNOS by Activation of NF-κB and MAP Kinases
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Enteropathogenic Escherichia coli (EPEC) infects the human intestinal epithelium and is a major cause of infantile diarrhea in developing countries. Nitric oxide (NO) is an important modulator of intestinal inflammatory response. The aim of the present study was to investigate whether EPEC outer membrane proteins (OMPs) up regulate epithelial cell expression of inducible nitric oxide synthase (iNOS) and to examine the role of NF-κB and MAP kinases (MAPK) on nitrite production. iNOS mRNA expression was assessed by RT-PCR. Nitrite levels were measured by Griess reaction. NF-κB activation by OMPs was evaluated by EMSA and immunoblotting was done to detect MAPK activation. EPEC OMP up regulated iNOS, induced nitrite production and NF-κB and MAPK were activated in caco-2 cells. The nitrite levels decreased when NF-κB and MAPK inhibitors were used. Thus, EPEC OMPs induce iNOS expression and NO production through activation of NF-κB and MAPK.
KeywordsEPEC iNOS nitric oxide outer membrane protein NF-κB MAP kinase
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- 6.de Grado, M., C. M. Rosenberger, A. Gauthier, B. A. Vallance, and B. B. Finlay. 2001. Enteropathogenic Escherichia coli infection induces expression of the early growth response factor by activating mitogen-activated protein kinase cascades in epithelial cells. Infect. Immun. 69:6217–6224.CrossRefPubMedGoogle Scholar
- 10.Rosenshine, I., M. Donnenberg, J. B. Kaper, and B. B. Finlay. 1992. Signal transduction between enteropathogenic Escherichia coli (EPEC) and epithelial cells: EPEC induces tyrosine phosphorylation of host cell proteins to initiate cytoskeletal rearrangement and bacterial uptake. EMBO J. 11:3551–3560.PubMedGoogle Scholar
- 18.Kumar, S. S., V. Malladi, K. Sankaran, R. Haigh, P. H. Williams, and A. Balakrishnan. 2001. Extrusion of actin-positive strands from HEp-2 and Int 407 cells caused by outer membrane preparations of enteropathogenic Escherichia coil and specific attachment of wild type bacteria to the Strands. Can. J. Microbiol. 47:727–734.CrossRefPubMedGoogle Scholar
- 23.Baldini, M. M., J. B. Kaper, M. M. Levine, D. C. Candy, and H. W. Moon. 1983. Plasmid-mediated adhesion in enteropathogenic Escherichia coli. J. Pediatr. Gastroenterol. Nutr. 2:534–538.Google Scholar
- 24.Donnenberg, M. S., and J. B. Kaper. 1991. Construction of an eae deletion mutant of enteropathogenic Escherichia coli by using a positive-selection suicide vector. Infect. Immun. 59:4310–4317.Google Scholar
- 33.Kim, J. M., J. S. Kim, H. C. Jung, I. S. Song, and C. Y. Kim. 2002. Up-regulation of inducible nitric oxide synthase and nitric oxide in Helicobacter pylori-infected human gastric epithelial cells: Possible role of interferon-γ in polarized nitric oxide secretion. Helicobacter 7:116–125.CrossRefPubMedGoogle Scholar