![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
B Activation
Department of Pharmacology (Y.J.C., C.C.C) and Division of Gastroenterology, Department of Internal Medicine (M.S.W., J.T.L.), College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (B.S.S.); Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (T.M.); and Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan (H.I.).
Gastric epithelial cells were incubated with a panel of clinical isolates of Helicobacter pylori, including nonulcer dyspepsia with gastritis (HS, n = 20), gastric ulcer (HU, n = 20), duodenal ulcer (HD, n = 21), and gastric cancer (HC, n = 20). HC strains induced a higher cyclooxygenase-2 (COX-2) expression than those from HS, HD, and HU. The bacterial virulence factors and the host cellular pathways were investigated. Virulence genes of iceA, vacA, babA2, cagA 3' repeat region, and hrgA failed to show any association with the disease status and COX-2 expression. Methylation-specific polymerase chain reaction revealed HC strains not affecting the methylation status of COX-2 promoter. Nuclear factor (NF)-
B, NF-interleukin 6, and cAMP response element were found to be involved in COX-2 induction. We explored a novel NF-B activation pathway. The mutants of TLR2 and TLR9, but not TLR4, inhibited H. pylori-induced COX-2 promoter activity, and neutralizing antibodies for TLR2 and TLR9 abolished H. pylori-induced COX-2 expression. Phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC), and Src inhibitors inhibited COX-2 induction. The dominant-negative mutants of NIK and various IB kinase complexes, including IKK
(Y188F), IKK (Y199F), and IKK (FF), inhibited the COX-2 promoter activity. Phosphorylation of GST-IKK (132-206) at Tyr188 and Tyr199 by c-Src was found after H. pylori infection. In summary, H. pylori induces COX-2 expression via activations of NF-B, NF-interleukin 6, the cAMP response element. In NF-B activation, H. pylori acts through TLR2/TLR9 to activate both the cascade of PI-PLC
/PKC
/c-Src/IKK/ and the cascade of NIK/IKK/, resulting in the IB degradation and the expression of COX-2 gene. The COX-2 overexpression may contribute to the carcinogenesis in patients colonized with these strains.
Address correspondence to: Dr. Ching-Chow Chen, Department of Pharmacology, College of Medicine, National Taiwan University, No.1, Jen-Ai Road, 1st Section, Taipei 10018, Taiwan. E-mail: ccchen{at}ha.mc.ntu.edu.tw
This article has been cited by other articles:
|
|
 |
|
  Y.-H. Wang, J.-J. Wu, and H.-Y. Lei The Autophagic Induction in Helicobacter pylori-Infected Macrophage Experimental Biology and Medicine, February 1, 2009; 234(2): 171 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I-T. Lee, S.-W. Wang, C.-W. Lee, C.-C. Chang, C.-C. Lin, S.-F. Luo, and C.-M. Yang Lipoteichoic Acid Induces HO-1 Expression via the TLR2/MyD88/c-Src/NADPH Oxidase Pathway and Nrf2 in Human Tracheal Smooth Muscle Cells J. Immunol., October 1, 2008; 181(7): 5098 - 5110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Slevogt, L. Maqami, K. Vardarowa, W. Beermann, A. C. Hocke, J. Eitel, B. Schmeck, A. Weimann, B. Opitz, S. Hippenstiel, et al. Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms Eur. Respir. J., April 1, 2008; 31(4): 725 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ueno, T. Koga, K. Kato, D. T. Golenbock, S. J. Gendler, H. Kai, and K. C. Kim MUC1 Mucin Is a Negative Regulator of Toll-Like Receptor Signaling Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 263 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hisatsune, E. Yamasaki, M. Nakayama, D. Shirasaka, H. Kurazono, Y. Katagata, H. Inoue, J. Han, J. Sap, K. Yahiro, et al. Helicobacter pylori VacA Enhances Prostaglandin E2 Production through Induction of Cyclooxygenase 2 Expression via a p38 Mitogen-Activated Protein Kinase/Activating Transcription Factor 2 Cascade in AZ-521 Cells Infect. Immun., September 1, 2007; 75(9): 4472 - 4481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Obonyo, M. Sabet, S. P. Cole, J. Ebmeyer, S. Uematsu, S. Akira, and D. G. Guiney Deficiencies of Myeloid Differentiation Factor 88, Toll-Like Receptor 2 (TLR2), or TLR4 Produce Specific Defects in Macrophage Cytokine Secretion Induced by Helicobacter pylori Infect. Immun., May 1, 2007; 75(5): 2408 - 2414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. T. Chiu, W. Y. Leung, M. P. Moyer, R. M. Strieter, and E. Rozengurt Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 production in nontransformed human colonic epithelial cells through NF-{kappa}B Am J Physiol Cell Physiol, February 1, 2007; 292(2): C767 - C777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. N'Guessan, M. O. Etouem, B. Schmeck, A. C. Hocke, S. Scharf, K. Vardarova, B. Opitz, A. Flieger, N. Suttorp, and S. Hippenstiel Legionella pneumophila-induced PKC{alpha}-, MAPK-, and NF-{kappa}B-dependent COX-2 expression in human lung epithelium Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L267 - L277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Damas, M. Jensenius, T. Ueland, K. Otterdal, A. Yndestad, S. S. Froland, J.-M. Rolain, B. Myrvang, D. Raoult, and P. Aukrust Increased Levels of Soluble CD40L in African Tick Bite Fever: Possible Involvement of TLRs in the Pathogenic Interaction between Rickettsia africae, Endothelial Cells, and Platelets J. Immunol., August 15, 2006; 177(4): 2699 - 2706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chun and A. Prince Activation of Ca2+-Dependent Signaling by TLR2 J. Immunol., July 15, 2006; 177(2): 1330 - 1337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Chang, M.-S. Wu, J.-T. Lin, and C.-C. Chen Helicobacter pylori-Induced Invasion and Angiogenesis of Gastric Cells Is Mediated by Cyclooxygenase-2 Induction through TLR2/TLR9 and Promoter Regulation J. Immunol., December 15, 2005; 175(12): 8242 - 8252. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
