Open AccessHelicobacter pylori Lipopolysaccharides Upregulate Toll-Like Receptor 4 Expression and Proliferation of Gastric Epithelial Cells via the MEK1/2-ERK1/2 Mitogen-Activated Protein Kinase Pathway
Author(s) -
Shinichi Yokota,
Tamaki Okabayashi,
Michael Rehli,
Nobuhiro Fujii,
Kenichi Amano
Publication year - 2010
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00903-09
Subject(s) - biology , tlr4 , tlr2 , helicobacter pylori , toll like receptor , lipopolysaccharide , kinase , signal transduction , protein kinase a , microbiology and biotechnology , receptor , mitogen activated protein kinase , immunology , innate immune system , biochemistry , genetics
Helicobacter pylori is recognized as an etiological agent of gastroduodenal diseases.H. pylori produces various toxic substances, including lipopolysaccharide (LPS). However,H. pylori LPS exhibits extremely weakly endotoxic activity compared to the typical LPS, such as that produced byEscherichia coli , which acts through Toll-like receptor 4 (TLR4) to induce inflammatory molecules. The gastric epithelial cell lines MKN28 and MKN45 express TLR4 at very low levels, so they show very weak interleukin-8 (IL-8) production in response toE. coli LPS, but pretreatment withH. pylori LPS markedly enhanced IL-8 production induced byE. coli LPS by upregulating TLR4 via TLR2 and the MEK1/2-ERK1/2 pathway. The transcription factor NF-Y was activated by this signal and promoted transcription of thetlr4 gene. These MEK1/2-ERK1/2 signal-mediated activities were more potently activated by LPS carrying a weakly antigenic epitope, which is frequently found in gastric cancers, than by LPS carrying a highly antigenic epitope, which is associated with chronic gastritis.H. pylori LPS also augmented the proliferation rate of gastric epithelial cells via the MEK1/2-ERK1/2 pathway.H. pylori LPS may be a pathogenic factor causing gastric tumors by enhancing cell proliferation and inflammation via the MEK1/2-ERK1/2 mitogen-activated protein kinase cascade in gastric epithelial cells.