| RRC ID |
43221
|
| 著者 |
Yamauchi K, Choi IJ, Lu H, Ogiwara H, Graham DY, Yamaoka Y.
|
| タイトル |
Regulation of IL-18 in Helicobacter pylori infection.
|
| ジャーナル |
J Immunol
|
| Abstract |
The gastric mucosal immune response is thought to be comprised predominantly of the Th1 type; however, there are limited data regarding the role of IL-18 in Helicobacter pylori-induced inflammation. We investigated IL-18 levels in gastric mucosal biopsy specimens as well as in isolated gastric epithelial cells and lamina propria mononuclear cells. We also investigated IL-18 levels in gastric epithelial cells and the monocyte cell line THP-1 cocultured with H. pylori. In both systems, IL-18 levels were markedly enhanced in H. pylori-infected epithelial cells and monocytes. IL-18 levels in H. pylori-infected gastric mucosa were well correlated with the severity of gastric inflammation, confirming that H. pylori-induced IL-18 plays an important role in gastric injury. Virulence factors of H. pylori; the cag pathogenicity island and OipA affected IL-18 induction in different manners. Up-regulation of IL-18 mRNA/protein in epithelial cells was dependent on both virulence factors. Interestingly, up-regulation of IL-18 mRNA in monocytes was independent of both factors, whereas IL-18 protein was OipA dependent-cag pathogenicity island independent, indicating that OipA regulates IL-18 induction in monocytes at the posttranscriptional level. IL-18 levels in the gastric biopsy specimens showed similar patterns to those in lamina propria mononuclear cells with respect to virulence factors, suggesting that submucosal monocytes/macrophages are the main source of IL-18 induced by H. pylori infection. H. pylori appeared to regulate the ERK/JNK-->AP-1 pathway in both cell types. In addition, OipA and its related p38 pathway may be closely involved in IL-18 induction in H. pylori-infected gastric mucosa and may contribute to gastric injury.
|
| 巻・号 |
180(2)
|
| ページ |
1207-16
|
| 公開日 |
2008-1-15
|
| DOI |
10.4049/jimmunol.180.2.1207
|
| PII |
180/2/1207
|
| PMID |
18178861
|
| PMC |
PMC2827480
|
| MeSH |
Antigens, Bacterial / metabolism*
Bacterial Outer Membrane Proteins / metabolism*
Bacterial Proteins / metabolism*
Cells, Cultured
Coculture Techniques
Gastric Mucosa / immunology*
Gastric Mucosa / microbiology
Gastric Mucosa / pathology
Helicobacter Infections / immunology*
Helicobacter Infections / microbiology
Helicobacter Infections / pathology
Helicobacter pylori / pathogenicity*
Humans
Interleukin-18 / genetics
Interleukin-18 / metabolism*
Luciferases / analysis
Luciferases / genetics
MAP Kinase Kinase Kinases / antagonists & inhibitors
MAP Kinase Kinase Kinases / metabolism
NF-kappa B / antagonists & inhibitors
NF-kappa B / metabolism
Promoter Regions, Genetic
RNA, Messenger / analysis
RNA, Messenger / metabolism
Sequence Deletion
Virulence Factors / metabolism*
|
| IF |
4.886
|
| 引用数 |
39
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MKN7(RCB0999)
MKN1(RCB1003)
MKN28(RCB1000)
MKN45(RCB1001)
Kato III(RCB2088) |