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

被引:33
作者
Hisatsune, Junzo
Yamasaki, Eiki
Nakayama, Masaaki
Shirasaka, Daisuke
Kurazono, Hisao
Katagata, Yohtaro
Inoue, Hiroyasu
Han, Jiahuai
Sap, Jan
Yahiro, Kinnosuke
Moss, Joel
Hirayama, Toshiya [1 ]
机构
[1] Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan
[2] Kobe Univ, Grad Sch Med, Div Digest Dis, Kobe, Hyogo 6500017, Japan
[3] Osaka Prefecture Univ, Grad Sch Life Sci & Environm Sci, Lab Vet Publ Hlth, Osaka 5998531, Japan
[4] Hirosaki Univ, Hirosaki, Aomori 0368561, Japan
[5] Nara Womens Univ, Dept Food & Nutr, Nara 6308506, Japan
[6] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[7] Univ Copenhagen, Dept Mol Pathol, DK-2100 Copenhagen, Denmark
[8] NHLBI, Pulm & Crit Care Med Branch, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1128/IAI.00500-07
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Treatment of AZ-521 cells with Helicobacter pylori VacA increased cyclooxygenase 2 (COX-2) mRNA in a time- and dose-dependent manner. A p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, blocked elevation of COX-2 mRNA levels, whereas PD98059, which blocks the Erk1/2 cascade, partially suppressed the increase. Consistent with involvement of p38 MAPK,, VacA-induced accumulation of COX-2 mRNA was reduced in AZ-521 cells overexpressing a dominant-negative p38 MAPK (DN-p38). Phosphatidylinositol-specific phospholipase C, which inhibits VacA-induced p38 MAPK activation, blocked VacA-induced COX-2 expression. In parallel with COX-2 expression, VacA increased prostaglandin E-2 (PGE(2)) production, which was inhibited by SB203580 and NS-398, a COX-2 inhibitor. VacA-induced PGE2 Production was markedly attenuated in AZ-521 cells stably expressing DN-p38. VacA increased transcription of a COX-2 promoter reporter gene and activated a COX-2 promoter containing mutated NF-kappa B or NF-interieukin-6 sites but not a mutated cis-acting replication element (CRE) site, suggesting direct involvement of the activating transcription factor 2 (ATF-2)/CREB-binding region in VacA-induced COX-2 promoter activation. The reduction of ATF-2 expression in AZ-521 cells transformed with ATF-2-small interfering RNA duplexes resulted in suppression of COX-2 expression. Thus, VacA enhances PGE2 production by AZ-521 cells through induction of COX-2 expression via the p38 MAPK/ATF-2 cascade, leading to activation of the CRE site in the COX-2 promoter.
引用
收藏
页码:4472 / 4481
页数:10
相关论文
共 60 条
[41]  
Ramsay RG, 2003, INT J IMMUNOPATH PH, V16, P59
[42]   A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA [J].
Ridley, SH ;
Dean, JLE ;
Sarsfield, SJ ;
Brook, M ;
Clark, AR ;
Saklatvala, J .
FEBS LETTERS, 1998, 439 (1-2) :75-80
[43]  
Ristimaki A, 1997, CANCER RES, V57, P1276
[44]   Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandin E2 synthesis in MKN 28 gastric mucosal cells in vitro [J].
Romano, M ;
Ricci, V ;
Memoli, A ;
Tuccillo, C ;
Di Popolo, A ;
Sommi, P ;
Acquaviva, AM ;
Blanco, CD ;
Bruni, CB ;
Zarrilli, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (44) :28560-28563
[45]   EPIDERMAL GROWTH-FACTOR IN BLOOD [J].
SAVAGE, AP ;
CHATTERJEE, VK ;
GREGORY, H ;
BLOOM, SR .
REGULATORY PEPTIDES, 1986, 16 (3-4) :199-206
[46]   Protein kinase D potentiates DNA synthesis induced by Gq-coupled receptors by increasing the duration of ERK signaling in swiss 3T3 cells [J].
Sinnett-Smith, J ;
Zhukova, E ;
Hsieh, N ;
Jiang, XH ;
Rozengurt, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (16) :16883-16893
[47]   Angiotensin II and epidermal growth factor induce cyclooxygenase-2 expression in intestinal epithelial cells through small GTPases using distinct signaling pathways [J].
Slice, LW ;
Chiu, T ;
Rozengurt, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (02) :1582-1593
[48]  
Subbaramaiah K, 1996, CANCER RES, V56, P4424
[49]   Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion [J].
Sundrud, MS ;
Torres, VJ ;
Unutmaz, D ;
Cover, TL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (20) :7727-7732
[50]   Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions [J].
Sung, JJY ;
Leung, WK ;
Go, MYY ;
To, KF ;
Cheng, ASL ;
Ng, EKW ;
Chan, FKL .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (03) :729-735