Arginase-1 and Treg Profile Appear to Modulate Inflammatory Process in Patients with Chronic Gastritis: IL-33 May Be the Alarm Cytokine in H. pylori-Positive Patients

Abstract

Helicobacter pylori (H. pylori) is a highly prevalent bacterium in our environment, directly involved in various upper digestive tract diseases, such as gastritis, peptic ulcer, and gastric cancer. Several molecules activating the immune system have been reported to be involved in containing H. pylori infection. This study is aimed at analyzing the mRNA expression of the cytokines IFN-γ, IL-17, IL-10, TGF-β, IL-6, IL-22, IL-23, and IL-33; transcription factors T-bet, RORC, and FOXP3; enzymes ARG1, ARG2, and NOS2; and neuropeptides VIP and TAC and their respective receptors VIPR1 and TACR1 in the stomach lining of patients with severe digestive disorders. One hundred and twenty six patients have been evaluated, presenting with symptoms in the upper digestive tract, with the clinical indication for an Upper Digestive Endoscopy exam. Two fragments of the mucosa of the gastric body and antrum have been collected for anatomopathological examination and to analyze the expression of enzymes, cytokines, and transcription factors using qPCR. Expression of the ARG1 gene was seen as significantly higher in the group of patients with chronic inactive gastritis than in the control group. Expression of the TGF-β gene and its FOXP3 transcription factor was significantly higher in the group of chronic inactive gastritis patients than in the control. Expression of IFN-γ, IL-17, IL-10, and TGF-β and the transcription factors, T-bet and RORC, in the presence or absence of H. pylori showed no significant difference. However, the expression of FOXP3 was significantly lower in H. pylori-positive patients than that in H. pylori-negative patients. ARG1 and Treg profile appeared to be modulating the inflammatory process, protecting patients from the tissue lesions with chronic inactive gastritis. Furthermore, we suggest that IL-33 may be a crucial mediator of the immune response against an infection, after gastric mucosal damage.

NOTCH1 is positively correlated with IL17F in Helicobacter pylori infection and a biomarker for mucosal injury

“… 18 However, it differed from the study of Da Silva et al. 25 Their findings showed that there were no significant differences in the expression of IL10 among chronic active gastritis patients, chronic inactive gastritis patients, or control cases, but the expression of FOXP3 in H. pylori -infected patients was significantly lower than that in non-infected patients. This discrepancy may be the reason that Treg cells are associated with VacA alleles, virulence factor and oipA status of H. pylori and histological grade.…”

The mitochondria-targeted sulfide delivery molecule attenuates drugs-induced gastropathy. Involvement of heme oxygenase pathway.

“…Restoration of GST-α level by AP39 confirmed our previous observation on ischemia/reperfusion-induced gastric injury [ 30 ]. ARG1 was shown to be upregulated in gastric mucosa of patients with inactive gastritis [ 86 ]. However, increased activity of ARG1 decreases l -arginine level.…”

Gastric alarmin release: A warning signal in the development of gastric mucosal diseases

“…Recent studies have suggested that IL-33 may be an alarmin in H. pylori -positive patients ( 135 ). IL-33 is highly expressed in the mucosa of patients with H. pylori -infected gastritis ( 136 ), and ST2 is recruited into membrane rafts in response to IL-33 release by H. pylori -infected gastric epithelial cells ( 137 ), which promotes the production of tumor necrosis factor-α (TNF-α) by MCs and inhibits the proliferation of gastric epithelial cells, leading to the progression of H. pylori -associated gastritis and bacterial colonization ( 138 ).…”