title: Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells.
abstract: BACKGROUND
  and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation.
  
  
  METHODS
  Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C-C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon gamma (IFN-gamma), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry.
  
  
  RESULTS
  MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN-gamma but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN-gamma secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related.
  
  
  CONCLUSIONS
  Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.
authors.affiliation: Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Futagami
authors.forename: T
authors.initials: T
authors.lastname: Hiratsuka
authors.forename: A
authors.initials: A
authors.lastname: Tatsuguchi
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Kusunoki
authors.forename: Y
authors.initials: Y
authors.lastname: Shinji
authors.forename: K
authors.initials: K
authors.lastname: Shinoki
authors.forename: T
authors.initials: T
authors.lastname: Iizumi
authors.forename: T
authors.initials: T
authors.lastname: Akamatsu
authors.forename: H
authors.initials: H
authors.lastname: Nishigaki
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: K
authors.initials: K
authors.lastname: Miyake
authors.forename: K
authors.initials: K
authors.lastname: Gudis
authors.forename: T
authors.initials: T
authors.lastname: Tsukui
authors.forename: C
authors.initials: C
authors.lastname: Sakamoto
mesh_terms: D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000502:physiology*; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000276:immunology; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism*; D005756:Gastritis / Q000276:immunology / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells / Q000378:metabolism / Q000382:microbiology; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism* / Q000382:microbiology
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases