Upregulation of MUC5AC production and deposition of Lewis determinants by Helicobacter pylori facilitate gastric tissue colonization and the maintenance of infection

Weronika Gonciarz , Maria Walencka , Anthony P. Moran , Krzysztof Hinc , Michał Obuchowski , Magdalena Chmiela

Abstract

Background: Helicobacter pylori bacteria colonize human gastric mucosa, cause chronic inflammation, peptic ulcers and gastric cancer. Colonization is mediated by H. pylori adhesins, which preferentially bind mucin 5 (MUC5AC) and Lewis (Le) determinants. The aim of this study was to evaluate the influence of H. pylori and their components on MUC5AC production and deposition of LeX/LeY in gastric epithelial cells in relation to bacterial adhesion using Caviae porcellus primary gastric epithelial cells and an in vivo model of experimental H. pylori infection in these animals. Methods: MUCA5C and LeX/LeY were induced in vitro by live H. pylori reference strain CCUG 17874 (2 × 107 CFU/ml), H. pylori glycine acid extract (GE), 10 μg/ml; cytotoxin associated gene A (CagA) protein, 1 μl/ml; UreA urease subunit, 5 μg/ml; lipopolysaccharide (LPS) 25 ng/ml and imaged by fluorescence microscopy after anti-MUC5AC or anti-LeX/LeY FITC antibody staining. Bacterial adhesion was imaged by using anti-H. pylori FITC antibodies. The animals were inoculated per os with H. pylori (3 times in 2 days intervals, 1 × 1010 CFU/ml). After 7 or 28 days an infection and inflammation were assessed by histological, serological and molecular methods. Gastric tissue sections of infected and control animals were screend for MUCA5C and LeX, and H. pylori adhesion as above. Results: MUC5AC production and deposition of Lewis determinants, especially LeX were upregulated in the milieu of live H. pylori as well as GE, CagA, UreA or LPS in vitro and in vivo during infection, more effectively in the acute (7 days) than in the chronic (28 days) phase of infection. This was related to enhanced adhesion of H. pylori, which was abrogated by anti-MUC5AC and anti-LeX or anti-LeY antibody treatment. Conclusions: Modulation of MUCA5C production and LeX/LeY deposition in the gastric mucosa by H. pylori can significantly increase gastric tissue colonization during H. pylori infection.
Autor Weronika Gonciarz
Weronika Gonciarz
-
, Maria Walencka
Maria Walencka
-
, Anthony P. Moran
Anthony P. Moran
-
, Krzysztof Hinc (MWB UG i GUMed / KBM)
Krzysztof Hinc
- Katedra Biotechnologii Medycznej (GUMed)
, Michał Obuchowski (MWB UG i GUMed / KBM)
Michał Obuchowski
- Katedra Biotechnologii Medycznej (GUMed)
, Magdalena Chmiela
Magdalena Chmiela
-
Tytuł czasopisma/seriiJournal of Biomedical Science, ISSN 1021-7770, (A 30 pkt)
Rok wydania2019
Tom26
Paginacja1-12
Objętość publikacji w arkuszach wydawniczych0.55
Numer artykułu23
Słowa kluczowe w języku angielskimMUC5AC, LewisX/Y, H. pylori, Guinea pigs
Klasyfikacja ASJC2736 Pharmacology (medical); 2704 Biochemistry, medical; 1307 Cell Biology; 1308 Clinical Biochemistry; 1312 Molecular Biology; 2700 General Medicine; 2712 Endocrinology, Diabetes and Metabolism
DOIDOI:10.1186/s12929-019-0515-z
URL https://rdcu.be/bEPct
Języken angielski
LicencjaCzasopismo (tylko dla artykułów); licence.documentVersion.FINAL_PUBLISHED; Uznanie Autorstwa (CC-BY); w dniu opublikowania
Punktacja (całkowita)30
PunktacjaPunktacja MNiSW = 30.0, 28-06-2019, ArticleFromJournal
Punktacja MNiSW (2013-2016) = 30.0, 28-06-2019, ArticleFromJournal
Wskaźniki publikacji Scopus SNIP (Source Normalised Impact per Paper): 2017 = 0.986; Impact Factor WoS: 2017 = 3.466 (2) - 2017=3.322 (5)
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