Helicobacter pylori antigens, acetylsalicylic acid, LDL and 7-ketocholesterol - their potential role in destabilizing the gastric epithelial cell barrier. An in vitro model of Kato III cells.

Abstract

Colonization of gastric tissue in humans by H. pylori Gram-negative bacteria initiates gastric and duodenal ulcers and even gastric cancers. Infections promote inflammation and damage to gastric epithelium which might be followed by the impairment of its barrier function. The role of H. pylori components in these processes has not been specified. H. pylori cytotoxicity may potentially increase in the milieu of anti-inflammatory drugs including acetylsalicylic acid (ASA). The lipid transport-associated molecule such as low density lipoprotein (LDL), which is a classic risk factor of coronary heart disease (CHD) and 7-ketocholesterol (7-kCh) a product of cholesterol oxidation, which may occur during the oxidative stress in LDL could also be considered as pro-inflammatory. The aim of this study was to evaluate the cytotoxicity of H. pylori antigens, ASA, LDL and 7-kCh towards Kato III gastric epithelial cells, on the basis of the cell ability to reduce tetrazolium salt (MTT) and morphology of cell nuclei assessed by 4',6-diamidino-2-phenylindole (DAPI) staining. Kato III cells were stimulated for 24 h, at 37°C and 5% CO2, with H. pylori antigens: cytotoxin associated gene A (CagA) protein, the urease A subunit (UreA), lipopolysaccharide (LPS) and ASA, LDL or 7-kCh. H. pylori LPS, ASA, LDL and 7-kCh, but not H. pylori glycine acid extract (GE), demonstrated cytotoxicity against Kato III cells, which was related to a diminished percentage of MTT reducing cells and to an increased cell population with the signs of DNA damage. The results suggest that damage to gastric epithelial cells can be induced independently by H. pylori antigens, ASA and endogenous lipid transport-associated molecules. During H. pylori infection in vivo, especially in CHD patients, synergistic or antagonistic interactions between these factors might possibly influence the disease course. Further study is necessary to explain these potential effects.

Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment

“…Chronic atrophic gastritis is a gastric premalignant condition (Sugano et al, 2015). Most cases of chronic atrophic gastritis are caused by persistent H. pylori infection (Sipponen and Maaroos, 2015), which triggers an inflammatory response that has various effects on gastric epithelial cells such as disruption of the gastric barrier (Gajewski et al, 2016), induction of apoptosis (Wan et al, 2016), and stimulation of proinflammatory cytokine secretion (Peek et al, 1995). Microbial composition in the stomach was shown to be altered in patients with chronic atrophic gastritis, with Helicobacteraceae, Streptococcaceae, Fusobacteriaceae, and Prevotellaceae as the major taxa (Parsons et al, 2017).…”

Role of NRF2 in protection of the gastrointestinal tract against oxidative stress

“…( 11 , 12 ) H. pylori colonization in GECs causes the accumulation of neutrophils and macrophages within the gastric mucosa, resulting in the generation of superoxide anion (O 2 − ) and nitric oxide (NO). ( 13 – 15 ) These conditions are histopathologically recognized as H. pylori -induced gastritis. Continuous release of free radicals from mucosal neutrophils accumulated within the H. pylori -infected gastric mucosa gradually results in GEC apoptosis, leading to gastric atrophy and intestinal metaplasia.…”

RecombinantHelicobacter pyloriCagA protein induces endoplasmic reticulum stress and autophagy in human cells

“…Therefore, CagA protein can be found in the extracellular matrix and directly interact with host human cells. Limited studies suggest that recombinant CagA can alter cell signaling activity, gene expression, and can induce cell death [34][35][36][37]. Targosz et al [34] treated the cells with a high level of exogenous CagA (10 µg/ml) while we used only 1 µg/ml of the protein for treatment in the present study.…”