RRC ID 39933
Author Maeda S, Akanuma M, Mitsuno Y, Hirata Y, Ogura K, Yoshida H, Shiratori Y, Omata M.
Title Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells.
Journal J. Biol. Chem.
Abstract NF-kappaB is a critical regulator of genes involved in inflammation. Gastric epithelial cells and macrophages are considered the main sources of pro-inflammatory cytokines. We investigated NF-kappaB activation by Helicobacter pylori in MKN45 gastric epithelial cells and THP-1 monocytic cells. Although, cag pathogenicity island (PAI)-positive H. pylori (wild type) activated NF-kappaB in both cells, isogenic mutant of cagE (DeltacagE) activated it only in THP-1 cells. Supernatant from the wild type culture could activate NF-kappaB in THP-1 cells but not in MKN45 cells. High density cDNA array analysis revealed that mRNA expression of NF-kappaB-regulated genes such as interleukin (IL)-8, tumor necrosis factor-alpha (TNFalpha), and IL-1beta was significantly up-regulated by the wild type in both cells, whereas it was up-regulated by DeltacagE only in THP-1 cells. Experiments using CD14-neutralizing antibody and IL-1 receptor-associated kinase (IRAK) assay showed that both wild type and DeltacagE H. pylori activated NF-kappaB through CD14 and IRAK in THP-1 cells but not in MKN45 cells. Macrophages from C3H/HeJ mice carrying point mutation in the Toll-like receptor 4 (TLR4) gene showed decreased NF-kappaB activation and TNFalpha secretion compared with C3H/HeN mouse macrophage when treated with H. pylori. In conclusion, H. pylori-induced NF-kappaB activation in epithelial cells is dependent on cag PAI and contact but does not involve CD14 and IRAK, whereas in macrophage/monocytic cells it is independent of cag PAI or contact but involves CD14 and TLR4.
Volume 276(48)
Pages 44856-64
Published 2001-11-30
DOI 10.1074/jbc.M105381200
PII M105381200
PMID 11546774
MeSH Animals Antibodies, Monoclonal / metabolism Cells, Cultured Ceramides / metabolism Cytokines / metabolism DNA, Complementary / metabolism Drosophila Proteins* Helicobacter pylori / metabolism* Humans Interleukin-1 / biosynthesis Interleukin-1 Receptor-Associated Kinases Interleukin-8 / biosynthesis Lipopolysaccharide Receptors / metabolism Male Membrane Glycoproteins / genetics Mice Mice, Inbred C3H Models, Biological Monocytes / metabolism* Monocytes / microbiology NF-kappa B / metabolism* Oligonucleotide Array Sequence Analysis Phosphorylation Point Mutation Protein Kinases / metabolism RNA, Messenger / metabolism Receptors, Cell Surface / genetics Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / metabolism* Stomach Neoplasms / microbiology Time Factors Toll-Like Receptor 4 Toll-Like Receptors Tumor Cells, Cultured Tumor Necrosis Factor-alpha / metabolism Up-Regulation
IF 4.011
Times Cited 138
Human and Animal Cells