IFN-gamma synergizes with TNF-alpha but not with viable H. pylori in up-regulating CXC chemokine secretion in gastric epithelial cells.
Helicobacter pylori colonizes the gastric epithelial surface and induces epithelial cells to increase production of the neutrophil attractant IL-8. Little is known about the role of the gastric epithelium in regulating mucosal T cell trafficking. We therefore characterized constitutive and regulated epithelial expression of the CXC chemokines IP-10, I-TAC and Mig, which specifically attract CXCR3 expressing CD4(+) T cells. Human gastric epithelial cell lines (AGS, Kato III, NCI) were used to characterize the constitutive and regulated expression of three CXC chemokines in response to IFN-gamma, TNF-alpha and different H. pylori preparations. Chemokine mRNA and protein production were measured by RT-PCR and ELISA. Gastric epithelial cells constitutively expressed mRNA for IP-10, Mig and I-TAC. IFN-gamma in combination with TNF-alpha strongly induced secretion of those chemokines. Soluble or membranous fractions of H. pylori significantly inhibited IFN-gamma/TNF-alpha induced epithelial cell IP-10 and Mig production. Gastric epithelial cells may contribute to mucosal T cell trafficking. The capacity of H. pylori products to inhibit IP-10 and Mig secretion may explain, at least in part, the failure to induce protective immunity against this bacterium and the ability of H. pylori to affect the presentation of the local inflammation.
Kraft
M
M
Department of Medicine B, University of Münster, Münster, Germany. kraftm@uni-muenster.de
Riedel
S
S
Maaser
C
C
Kucharzik
T
T
Steinbuechel
A
A
Domschke
W
W
Luegering
N
N
D002460:Cell Line; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D004357:Drug Synergism; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D018928:Immunity, Mucosal; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma