Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag- Helicobacter pylori.

2.50
Hdl Handle:
http://hdl.handle.net/2436/8018
Title:
Differential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag- Helicobacter pylori.
Authors:
Keates, Sarah; Keates, Andrew C.; Warny, Michel; Peek, Richard M.; Murray, Paul G.; Kelly, Ciaran P.
Abstract:
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 microM; MAP kinase kinase (MEK-1) inhibitor) and SB203580 (10 microM; 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 IkappaBalpha degradation or NF-kappaB 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-kappaB 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.
Citation:
The Journal of Immunology, 163(10): 5552-5559
Publisher:
American Association of Immunologists
Issue Date:
1999
URI:
http://hdl.handle.net/2436/8018
PubMed ID:
10553083
Additional Links:
http://www.jimmunol.org/cgi/reprint/163/10/5552
Submitted date:
2007-01-29
Type:
Article
Language:
en
ISSN:
0022-1767; 1550-6606
Appears in Collections:
Sport, Exercise and Health Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorKeates, Sarah-
dc.contributor.authorKeates, Andrew C.-
dc.contributor.authorWarny, Michel-
dc.contributor.authorPeek, Richard M.-
dc.contributor.authorMurray, Paul G.-
dc.contributor.authorKelly, Ciaran P.-
dc.date.accessioned2007-01-31T16:18:46Z-
dc.date.available2007-01-31T16:18:46Z-
dc.date.issued1999-
dc.date.submitted2007-01-29-
dc.identifier.citationThe Journal of Immunology, 163(10): 5552-5559en
dc.identifier.issn0022-1767-
dc.identifier.issn1550-6606-
dc.identifier.pmid10553083-
dc.identifier.urihttp://hdl.handle.net/2436/8018-
dc.description.abstractThe 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 microM; MAP kinase kinase (MEK-1) inhibitor) and SB203580 (10 microM; 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 IkappaBalpha degradation or NF-kappaB 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-kappaB 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.en
dc.format.extent950962 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoenen
dc.publisherAmerican Association of Immunologistsen
dc.relation.urlhttp://www.jimmunol.org/cgi/reprint/163/10/5552en
dc.subjectDifferential activationen
dc.subjectMitogen-activated protein kinasesen
dc.subjectHelicobacter pylorien
dc.subjectMAPen
dc.subjectGastric epithelial cellsen
dc.titleDifferential activation of mitogen-activated protein kinases in AGS gastric epithelial cells by cag+ and cag- Helicobacter pylori.en
dc.typeArticleen
dc.format.digYES-
All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.