RRC ID 43221
Author Yamauchi K, Choi IJ, Lu H, Ogiwara H, Graham DY, Yamaoka Y.
Title Regulation of IL-18 in Helicobacter pylori infection.
Journal 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.
Volume 180(2)
Pages 1207-16
Published 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
Times Cited 39
Human and Animal Cells