Background Helicobacter pylori colonizes the human gastric mucosa, causing chronic inflammation, peptic ulcers and gastric cancer. A cascade of harmful processes results from the interaction of these bacteria with the gastric epithelium. Aim To investigate these processes in terms of upregulation of oxidative stress and cell apoptosis and downregulation of the pro-regenerative activity of cells. Methods We employed an in vivo guinea pig model at 7 or 28 days postinoculation with H . pylori , corresponding to an acute or chronic stage of infection, respectively, and an in vitro model of guinea pig primary gastric epithelial cells and fibroblasts treated with bacterial components: glycine acid extract (GE), urease subunit A (UreA), cytotoxin-associated gene A protein (CagA) and lipopolysaccharide (LPS). Cells were evaluated for metabolic activity (MTT reduction), myeloperoxidase (MPO) and metalloproteinase (MMP-9) secretion, lipid peroxidation (4-hydroxynonenal (4HNE)), migration (wound healing), proliferation (Ki-67 antigen) and cell apoptosis (TUNEL assay; Bcl-xL, Bax, Bcl-2 expression; caspase 3 cleavage). Results Significant infiltration of the gastric mucosa by inflammatory cells in vivo in response to H . pylori was accompanied by oxidative stress and cell apoptosis, which were more intense 7 than 28 days after inoculation. The increase in cell proliferation was more intense in chronic than acute infection. H . pylori components GE, CagA, UreA, and LPS upregulated oxidative stress and apoptosis. Only H . pylori LPS inhibited cell migration and proliferation, which was accompanied by the upregulation of MMP-9. Conclusions H . pylori infection induces cell apoptosis in conjunction with increased oxidative stress. Elevated apoptosis protects against deleterious inflammation and neoplasia; however, it reduces cell integrity. Upregulation of cell migration and proliferation in response to injury in the milieu of GE, CagA or UreA facilitates tissue regeneration but increases the risk of neoplasia. By comparison, downregulation of cell regeneration by H . pylori LPS may promote chronic inflammation.

AIMTo determine the impact of selected well defined Helicobacter pylori (H. pylori) antigens on gastric barrier cell turnover.METHODSIn this study, using two cellular models of gastric epithelial cells and fibroblasts, we have focused on exploring the effects of well defined H. pylori soluble components such as glycine acid extract antigenic complex (GE), subunit A of urease (UreA), cytotoxin associated gene A protein (CagA) and lipopolysaccharide (LPS) on cell turnover by comparing the wound healing capacity of the cells in terms of their proliferative and metabolic activity as well as cell cycle distribution. Toxic effects of H. pylori components have been assessed in an association with damage to cell nuclei and inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation.RESULTSWe showed that H. pylori GE, CagA and UreA promoted regeneration of epithelial cells and fibroblasts, which is necessary for effective tissue healing. However, in vivo increased proliferative activity of these cells may constitute an increased risk of gastric neoplasia. In contrast, H. pylori LPS showed a dose-dependent influence on the process of wound healing. At a low concentration (1 ng/mL) H. pylori LPS accelerated of healing epithelial cells, which was linked to significantly enhanced cell proliferation and MTT reduction as well as lack of alterations in cell cycle and downregulation of epidermal growth factor (EGF) production as well as cell nuclei destruction. By comparison, H. pylori LPS at a high concentration (25 ng/mL) inhibited the process of wound repair, which was related to diminished proliferative activity of the cells, cell cycle arrest, destruction of cell nuclei and downregulation of the EGF/STAT3 signalling pathway.CONCLUSIONIn vivo H. pylori LPS driven effects might lead to the maintenance of chronic inflammatory response and pathological disorders on the level of the gastric mucosal barrier.

In this review, we discussed the findings and concepts underlying the potential role of Helicobacter pylori (H. pylori) infections in the initiation, development or persistence of atherosclerosis and coronary heart disease (CHD). This Gram-negative bacterium was described by Marshall and Warren in 1984. The majority of infected subjects carries and transmits H. pylori with no symptoms; however, in some individuals these bacteria may cause peptic ulcers, and even gastric cancers. The widespread prevalence of H. pylori infections and the fact that frequently they remain asymptomatic may suggest that, similarly to intestinal microflora, H. pylori may deliver antigens that stimulate not only local, but also systemic inflammatory response. Recently, possible association between H. pylori infection and extragastric disorders has been suggested. Knowledge on the etiology of atherosclerosis together with current findings in the area of H. pylori infections constitute the background for the newly proposed hypothesis that those two processes may be related. Many research studies confirm the indirect association between the prevalence of H. pylori and the occurrence of CHD. According to majority of findings the involvement of H. pylori in this process is based on the chronic inflammation which might facilitate the CHD-related pathologies. It needs to be elucidated, if the infection initiate or just accelerate the formation of atheromatous plaque.

Helicobacter pylori is an etiological agent of chronic gastritis, gastric and duodenal ulcers and gastric cancers. The use of an appropriate animal model for experimental studies on the pathogenesis of H. pylori infections is necessary due to the chronic character of such infections and difficulties in identifying their early stage in humans. The aim of this study was to develop a guinea pig model of H. pylori infection and identify its microbiological, histological, serological and molecular determinants. Guinea pigs were inoculated per os with H. pylori strains: CCUG 17874 or ATCC 700312, both producing vacuolating cytotoxin A (VacA) and cytotoxin associated gene A (CagA) protein, suspended in Brucella broth with fetal calf serum (FCS) and Skirrow supplement of antibiotics. To determine H. pylori colonization, 7 and 28 days after the challenge, a panel of diagnostic methods was used. It included culturing of microorganisms from the gastric tissue, histopathological analysis of gastric sections, stained by Mayer,s haematoxylin and eosin to assess inflammatory response, by Giemsa as well as Warthin-Starry silver staining to visualise Helicobacter-like organisms (HLO) and with anti-Ki-67 antigen to assess epithelial cell proliferation. H. pylori infection was also confirmed by polymerase chain reactions (PCR) for detection in gastric tissue of ureC and cagA genes and by serological assessment of H. pylori antigens in faeces. This study showed the usefulness of microbiological, histological, immunological and molecular methods for the detection of persistent H. pylori infections in guinea pigs, which could be an appropriate model for studying H. pylori pathogenesis and the related immune response against these microbes.

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