Inflammatory signaling pathways induced by Helicobacter pylori in primary human gastric epithelial cells

• Published in: Innate immunity (London, England) England), 2017-02, Vol.23 (2), p.165-174
• Main Authors: Tran, Cong Tri, Garcia, Magali, Garnier, Martine, Burucoa, Christophe, Bodet, Charles
• Format: Article
• Language: English
• Subjects: Antibodies, Blocking - pharmacology; Bacteriology; Cells, Cultured; Chemokine CXCL1 - genetics; Chemokine CXCL1 - metabolism; Chemokine CXCL5 - genetics; Chemokine CXCL5 - metabolism; Epithelial Cells - immunology; Epithelial Cells - microbiology; ErbB Receptors - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Helicobacter Infections - immunology; Helicobacter pylori - immunology; Humans; Immunology; Inflammation Mediators - metabolism; Innate immunity; Interleukin-8 - genetics; Interleukin-8 - metabolism; Janus Kinases - metabolism; Life Sciences; Microbiology and Parasitology; Primary Cell Culture; Signal Transduction; Stomach - pathology; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - immunology; Toll-Like Receptor 4 - metabolism
• ISSN: 1753-4259; 1662-811X; 1753-4267; 1662-8128
• DOI: 10.1177/1753425916681077

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 B128ΔcagM, 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.