Differential effects of multiplicity of infection on Helicobacter pylori-induced signaling pathways and interleukin-8 gene transcription.
Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA ( + ) strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.
Ritter
Birgit
B
Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Ritter.Birgit@MH-Hannover.de
Kilian
Petra
P
Reboll
Marc Rene
MR
Resch
Klaus
K
DiStefano
Johanna Kay
JK
Frank
Ronald
R
Beil
Winfried
W
Nourbakhsh
Mahtab
M
D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004381:Duodenal Ulcer / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction; D013270:Stomach / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D037521:Virulence Factors; D020929:Mitogen-Activated Protein Kinase Kinases