Expression of HLA-DR, costimulatory molecules B7-1, B7-2, intercellular adhesion molecule-1 (ICAM-1) and Fas ligand (FasL) on gastric epithelial cells inHelicobacter pylorigastritis; influence ofH. pylorieradication

Abstract

SUMMARYThere is evidence that Helicobacter pylori infection up-regulates the expression of HLA class II molecules by gastric epithelial cells (GEC). In this study we evaluated whether GEC are capable of expression of costimulatory molecules in H. pylori gastritis. The expression of FasL by GEC, before and after eradication of H. pylori, was also studied. Thirty patients (23 men) aged 27±81 years (53´67^13´99 years (mean^s.d.)) with dyspepsia were studied. Upper gastrointestinal endoscopy was performed and six biopsies were obtained (antrum, n 3; corpus, n 3) for Campylobacter-Like Organisms (CLO) test and histology; 23 (16 men) were H. pylori 1 and seven (all men) were H. pylori 2 by both methods and served as controls. Helicobacter pylori eradication therapy was given to H. pylori 1 patients and all patients were re-endoscoped after 116^9 days. Formalin-fixed paraffin-embedded tissue sections were stained by the ABC immunoalkaline phosphatase method. In H. pylori gastritis HLA-DR was expressed and correlated with disease activity (P , 0´01). No HLA-DR was observed in controls. In H. pylori-eradicated patients significant decrease of HLA-DR was found (antrum, P , 0´001). ICAM-1 was expressed by GEC in 80% of H. pylori 1 patients; ICAM-1 expression did not correlate with gastritis parameters and decreased significantly after eradication (antrum, P , 0´01). B7-1 and B7-2 were expressed on H. pylori 1 samples and their expression decreased after eradication, albeit not significantly. Weak epithelial expression of both B7 molecules was observed in all the controls. FasL was steadily expressed by GEC in both H. pylori 1 and H. pylori 2 patients and remained almost unchanged after eradication. These findings suggest that GEC may acquire antigen-presenting cell properties in H. pylori infection through de novo expression of HLA-DR and costimulatory molecules. This seems to be attenuated after eradication and resolution of mucosal inflammation. The same cells exhibit the capacity to control the inflammatory process, probably by inducing apoptotic cell death to Fas-bearing infiltrating lymphocytes.

Major Histocompatibility Complex Class II Inhibits Fas Antigen-Mediated Gastric Mucosal Cell Apoptosis through Actin-Dependent Inhibition of Receptor Aggregation

“…This differential expression of Fas Ag and MHCII within the gastric mucosa creates the potential for receptor interaction and variable signaling outcomes. MHCII is expressed in metaplastic and dysplastic tissue (unpublished observation) as well as in carcinoma (1,7,48), making a scenario of MHCII/Fas Ag receptor interaction plausible.…”

“…During Helicobacter infection, gastric mucosal cells upregulate surface MHCII expression and costimulatory molecules (1,15,16,53) and have the ability to weakly present antigens (1,47). Additionally, there is evidence that Helicobacter pylori may bind the gastric cell via the MHCII complex and regulate apoptotic responses (15).…”

Helicobacter pyloriPersistence: an Overview of Interactions betweenH. pyloriand Host Immune Defenses

“…Therefore, there is some uncertainty about the location where priming of the immune response to H. pylori occurs. Gastric epithelial cells up-regulate expression of major histocompatibility complex (MHC) class II and costimulatory molecules during H. pylori infection (17,255), and potentially these cells have a role in antigen presentation. Monocytes, macrophages, and dendritic cells in the lamina propria of the gastric mucosa also may play important roles in antigen presentation (115,222,240).…”

Biomarkers in Patients with Gastric Inflammation: A Systematic Review

“…Several studies have demonstrated the overexpression of HLA class II molecules in gastric mucosa [140,141,142,143,144,145,146] and circulating mononuclear cells [147] in patients with gastric inflammation. It has been reported that gastric epithelial cells as well as classical APCs such as macrophages express HLA-DR, -DP, and -DQ [141,142,143,144], and that the extent of epithelial HLA-DR expression is parallel with the degree of inflammation [141, 146] and activity [146].…”

“…It has been reported that gastric epithelial cells as well as classical APCs such as macrophages express HLA-DR, -DP, and -DQ [141,142,143,144], and that the extent of epithelial HLA-DR expression is parallel with the degree of inflammation [141, 146] and activity [146]. On the other hand, the expression of HLA-DR was not increased in the lamina propria of gastric mucosa infected with H. pylori [144].…”