title: Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells.
abstract: Inflammatory signaling pathways induced by Helicobacter pylori remain unclear, having been studied mostly on cell-line models derived from gastric adenocarcinoma with potentially altered signaling pathways and nonfunctional receptors. Here, H. pylori-induced signaling pathways were investigated in primary human gastric epithelial cells. Inflammatory response was analyzed on chemokine mRNA expression and production after infection of gastric epithelial cells by H. pylori strains, B128 and B128Δ cagM, a cag type IV secretion system defective strain. Signaling pathway involvement was investigated using inhibitors of epidermal growth factor receptor (EGFR), MAPK, JAK and blocking Abs against TLR2 and TLR4. Inhibitors of EGFR, MAPK and JAK significantly reduced the chemokine mRNA expression and production induced by both H. pylori strains at 3 h and 24 h post-infection. JNK inhibitor reduced chemokine production at 24 h post-infection. Blocking Abs against TLR2 but not TLR4 showed significant reduction of chemokine secretion. Using primary culture of human gastric epithelial cells, our data suggest that H. pylori can be recognized by TLR2, leading to chemokine induction, and that EGFR, MAPK and the JAK/STAT signaling pathways play a key role in the H. pylori-induced CXCL1, CXCL5 and CXCL8 response in a cag pathogenicity island-independent manner.
authors.affiliation: 1 Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC - EA 4331), Université de Poitiers, Poitiers, France.|2 Laboratoire de Bactériologie Hygiène, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Cong Tri
authors.initials: CT
authors.lastname: Tran
authors.affiliation: 1 Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC - EA 4331), Université de Poitiers, Poitiers, France.|2 Laboratoire de Bactériologie Hygiène, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Garcia
authors.affiliation: 1 Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC - EA 4331), Université de Poitiers, Poitiers, France.|2 Laboratoire de Bactériologie Hygiène, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Garnier
authors.affiliation: 1 Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC - EA 4331), Université de Poitiers, Poitiers, France.|2 Laboratoire de Bactériologie Hygiène, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Burucoa
authors.affiliation: 1 Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC - EA 4331), Université de Poitiers, Poitiers, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Bodet
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D061251:Primary Cell Culture; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018836:Inflammation Mediators; D016209:Interleukin-8; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C512478:EGFR protein, human; D066246:ErbB Receptors; D053612:Janus Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: EGFR; Helicobacter pylori; TLR2; cag pathogenicity island; primary gastric epithelial cells