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*
Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215;
Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN 37232; and
School of Health Sciences, University of Wolverhampton, Wolverhampton, United Kingdom
The aim of this study was to determine whether Helicobacter
pylori activates mitogen-activated protein (MAP) kinases in
gastric epithelial cells. Infection of AGS cells with an H.
pylori cag+ strain rapidly (5 min) induced a
dose-dependent activation of extracellular signal-regulated kinases
(ERK), p38, and c-Jun N-terminal kinase (JNK) MAP kinases, as
determined by Western blot analysis and in vitro kinase assay. Compared
with cag+ strains,
cag- clinical isolates were less potent in
inducing MAP kinase, particularly JNK and p38, activation. Isogenic
inactivation of the picB region of the
cag pathogenicity island resulted in a similar loss of
JNK and p38 MAP kinase activation. The specific MAP kinase inhibitors,
PD98059 (25 µM; MAP kinase kinase (MEK-1) inhibitor) and SB203580 (10
µM; p38 inhibitor), reduced H. pylori-induced IL-8
production in AGS cells by 78 and 82%, respectively
(p < 0.01 for each). Both inhibitors together
completely blocked IL-8 production (p < 0.001).
However, the MAP kinase inhibitors did not prevent H.
pylori-induced I
B
degradation or NF-B activation.
Thus, H. pylori rapidly activates ERK, p38, and JNK MAP
kinases in gastric epithelial cells; cag+
isolates are more potent than cag- strains
in inducing MAP kinase phosphorylation and gene products of the
cag pathogenicity island are required for maximal MAP
kinase activation. p38 and MEK-1 activity are required for H.
pylori-induced IL-8 production, but do not appear to be
essential for H. pylori-induced NF-B activation.
Since MAP kinases regulate cell proliferation, differentiation,
programmed death, stress, and inflammatory responses, activation of
gastric epithelial cell MAP kinases by H. pylori
cag+ strains may be instrumental in inducing
gastroduodenal inflammation, ulceration, and
neoplasia.
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|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
 |
|
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|
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|
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|
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|
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S. D. Savkovic, A. Ramaswamy, A. Koutsouris, and G. Hecht EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption Am J Physiol Gastrointest Liver Physiol, October 1, 2001; 281(4): G890 - G898. [Abstract] [Full Text] [PDF]
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G. Le'Negrate, V. Ricci, V. Hofman, B. Mograbi, P. Hofman, and B. Rossi Epithelial Intestinal Cell Apoptosis Induced by Helicobacter pylori Depends on Expression of the cag Pathogenicity Island Phenotype Infect. Immun., August 1, 2001; 69(8): 5001 - 5009. [Abstract] [Full Text] [PDF]
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 A. Masamune, M. Yoshida, Y. Sakai, and T. Shimosegawa Rebamipide Inhibits Ceramide-Induced Interleukin-8 Production in Kato III Human Gastric Cancer Cells J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 485 - 492. [Abstract] [Full Text] [PDF]
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A. Banan, J. Z. Fields, Y. Zhang, and A. Keshavarzian Phospholipase C-{gamma} inhibition prevents EGF protection of intestinal cytoskeleton and barrier against oxidants Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G412 - G423. [Abstract] [Full Text] [PDF]
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Y. Hirata, S. Maeda, Y. Mitsuno, M. Akanuma, Y. Yamaji, K. Ogura, H. Yoshida, Y. Shiratori, and M. Omata Helicobacter pylori Activates the Cyclin D1 Gene through Mitogen- Activated Protein Kinase Pathway in Gastric Cancer Cells Infect. Immun., June 1, 2001; 69(6): 3965 - 3971. [Abstract] [Full Text] [PDF]
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R. M. Peek Jr. Microbes and Microbial Toxins: Paradigms for Microbial-Mucosal Interactions: IV. Helicobacter pylori strain-specific activation of signal transduction cascades related to gastric inflammation Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G525 - G530. [Abstract] [Full Text] [PDF]
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C. Audibert, C. Burucoa, B. Janvier, and J. L. Fauchere Implication of the Structure of the Helicobacter pylori cag Pathogenicity Island in Induction of Interleukin-8 Secretion Infect. Immun., March 1, 2001; 69(3): 1625 - 1629. [Abstract] [Full Text] [PDF]
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S. Takahashi, Y. Keto, T. Fujita, T. Uchiyama, and A. Yamamoto FR167653, a p38 Mitogen-Activated Protein Kinase Inhibitor, Prevents Helicobacter pylori-Induced Gastritis in Mongolian Gerbils J. Pharmacol. Exp. Ther., January 1, 2001; 296(1): 48 - 56. [Abstract] [Full Text]
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T. Pomorski, T. F. Meyer, and M. Naumann Helicobacter pylori-induced Prostaglandin E2 Synthesis Involves Activation of Cytosolic Phospholipase A2 in Epithelial Cells J. Biol. Chem., January 5, 2001; 276(1): 804 - 810. [Abstract] [Full Text] [PDF]
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R. A. Gupta, D. B. Polk, U. Krishna, D. A. Israel, F. Yan, R. N. DuBois, and R. M. Peek Jr. Activation of Peroxisome Proliferator-activated Receptor gamma Suppresses Nuclear Factor kappa B-mediated Apoptosis Induced by Helicobacter pylori in Gastric Epithelial Cells J. Biol. Chem., August 10, 2001; 276(33): 31059 - 31066. [Abstract] [Full Text] [PDF]
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D. Zhao, A. C. Keates, S. Kuhnt-Moore, M. P. Moyer, C. P. Kelly, and C. Pothoulakis Signal Transduction Pathways Mediating Neurotensin-stimulated Interleukin-8 Expression in Human Colonocytes J. Biol. Chem., November 21, 2001; 276(48): 44464 - 44471. [Abstract] [Full Text] [PDF]
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J.-R. Basque, P. Chailler, and D. Menard Laminins and TGF-beta maintain cell polarity and functionality of human gastric glandular epithelium Am J Physiol Cell Physiol, April 1, 2002; 282(4): C873 - C884. [Abstract] [Full Text] [PDF]
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