| RRC ID |
39933
|
| 著者 |
Maeda S, Akanuma M, Mitsuno Y, Hirata Y, Ogura K, Yoshida H, Shiratori Y, Omata M.
|
| タイトル |
Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells.
|
| ジャーナル |
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.
|
| 巻・号 |
276(48)
|
| ページ |
44856-64
|
| 公開日 |
2001-11-30
|
| DOI |
10.1074/jbc.M105381200
|
| PII |
S0021-9258(19)82688-1
|
| 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 |
4.238
|
| 引用数 |
157
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MKN45
J774 |
