Different effectiveness of helicobacter pylori lipopolysaccharides with or without lewisxy determinants in stimulating the secretion of proinflammatory cytokines il-8 and tnf-α by peripheral blood mononuclear leukocytes

Abstract

Introduction: Helicobacter pylori is an aetiological agent of chronic gastritis, gastric and duodenal ulcers, and gastric cancers. It is suggested that H. pylori must have undergone evolutionary changes that enable the bacteria to overcome the host immune response. The molecular mimicry between Lewis (Le) determinants present in H. pylori lipopolysaccharide (LPS) and on the host cells may play a role in the outcome of H. pylori infections. Aim: In this study we investigated the production of inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 8 (IL-8), by human peripheral blood mononuclear leukocytes (PBML) from H. pylori infected (11) and uninfected (10) subjects (21 women, aged 25-50 years), in response to H. pylori-LPS with LeXY(+) or without LeXY(-) determinants. Material and methods: Peripheral blood was collected using the Vacutainer heparin system and constituted a source of total or monocyte and lymphocyte enriched PBML fractions. Tumour necrosis factor alpha and IL-8 were assessed by immunosorbent assay (ELISA) in the supernatants from leukocyte cultures stimulated or not with H. pylon LPS or standard Escherichia coli LPS. Results: The results showed that adherent but not non-adherent PBML responded to H. pylori-LPS by TNF-alpha and IL-8 production. The H. pylori-LPS LeXY(+) was a stronger stimulus for macrophage-derived cytokines, as compared with H. pylori-LPS LeXY(-). Helicobacter pylori-LPS LeXY(+) driven production of TNF-alpha and IL-8 was significantly inhibited with antibodies to LPS-binding protein (LBP) and to CD14 proteins. Conclusions: It is possible that LeXY determinants of H. pylori-LPS could be involved in LPS signalling for inflammatory cytokines and thus regulate the outcome of H. pylon infections.