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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.
- Source :
- Hisatsune , J , Yamasaki , E , Nakayama , M , Shirasaka , D , Kurazono , H , Katagata , Y , Inoue , H , Han , J , Sap , J , Yahiro , K , Moss , J & Hirayama , T 2007 , ' 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. ' , Infection and Immunity , vol. 75 , no. 9 , pp. 4472-81 .
- Publication Year :
- 2007
-
Abstract
- Udgivelsesdato: 2007-Sep<br />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 PGE(2) 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-kappaB or NF-interleukin-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 PGE(2) 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.
Details
- Database :
- OAIster
- Journal :
- Hisatsune , J , Yamasaki , E , Nakayama , M , Shirasaka , D , Kurazono , H , Katagata , Y , Inoue , H , Han , J , Sap , J , Yahiro , K , Moss , J & Hirayama , T 2007 , ' 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. ' , Infection and Immunity , vol. 75 , no. 9 , pp. 4472-81 .
- Notes :
- English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1322548761
- Document Type :
- Electronic Resource