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
[1]   Epigenetic determination of a cell-specific gene expression program by ATF-2 and the histone variant macroH2A [J].
Agelopoulos, Marios ;
Thanos, Dimitris .
EMBO JOURNAL, 2006, 25 (20) :4843-4853
[2]   Resistance of primary murine CD4+ T cells to Helicobacter pylori vacuolating cytotoxin [J].
Algood, Holly M. Scott ;
Torres, Victor J. ;
Unutmaz, Derya ;
Cover, Timothy L. .
INFECTION AND IMMUNITY, 2007, 75 (01) :334-341
[3]  
Axon AT, 1999, GUT S1, V45, P11
[4]   The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms [J].
Boncristiano, M ;
Paccani, SR ;
Barone, S ;
Ulivieri, C ;
Patrussi, L ;
Ilver, D ;
Amedei, A ;
D'Elios, MM ;
Telford, JL ;
Baldari, CT .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) :1887-1897
[5]   Cyclooxygenase as a target in lung cancer [J].
Brown, JR ;
DuBois, RN .
CLINICAL CANCER RESEARCH, 2004, 10 (12) :4266S-4269S
[6]   Helicobacter pylori γ-glutamyltranspeptidase upregulates COX-2 and EGF-related peptide expression in human gastric cells [J].
Busiello, I ;
Acquaviva, R ;
Di Popolo, A ;
Blanchard, TG ;
Ricci, V ;
Romano, M ;
Zarrilli, R .
CELLULAR MICROBIOLOGY, 2004, 6 (03) :255-267
[7]  
Caputo R, 2003, CLIN CANCER RES, V9, P2015
[8]   Mammalian MAP kinase signalling cascades [J].
Chang, LF ;
Karin, M .
NATURE, 2001, 410 (6824) :37-40
[9]   Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-κB activation [J].
Chang, YJ ;
Wu, MS ;
Lin, JT ;
Sheu, BS ;
Muta, T ;
Inoue, H ;
Chen, CC .
MOLECULAR PHARMACOLOGY, 2004, 66 (06) :1465-1477
[10]   Clinicopathologic association of cyclooxygenase 1 and cyclooxygenase 2 expression in gastric adenocarcinoma [J].
Chen, CN ;
Sung, CT ;
Lin, MT ;
Lee, PH ;
Chang, KJ .
ANNALS OF SURGERY, 2001, 233 (02) :183-188