Abstract
Helicobacter pylori infection has been associated with the onset of gastric mucosal inflammation and is known to perturb the balance between T-regulatory (Treg) and T-helper 17 (Th17) cells which causes a spurt of interleukin 17 (IL17) and transforming growth factor-β (TGF-β) from Th17 and Treg cells within the gastric milieu. IL17 instigates a surge of interleukin 6 (IL6) from T-helper 1 (Th1) and T-helper 2 (Th2) cells. Further, H. pylori infection is known to stimulate the atypical DNA methylation in gastric mucosa. However, the precise role of cytokine signaling in induction of epigenetic modifications during gastric carcinogenesis is vaguely understood. In this study, patient samples from were examined using real-time polymerase chain reaction (qPCR), PCR, methylation-specific (MS)-PCR, and enzyme-linked immunosorbent assays. We found that H. pylori infection augments the production of interleukin 10 (IL10), IL6, and TGF-β in the gastric milieu and systemic circulation. Together with the IL6/IL10 mediated hyperactivation of the JAK/STAT pathway, H. pylori infection causes the inactivation of suppressor of cytokine signaling 1 (SOCS1) gene through the hypermethylation of the promoter region. This study signifies that H. pylori-mediated epigenetic silencing of SOCS1 in concert with inflammatory cytokines miffs hyperactivation of the JAK/STAT cascade during gastric carcinogenesis.
Highlights
Gastric cancer arises as a consequence of series of genetic, epigenetic and metabolic alteration in the mucus-producing cells on the inner surface of the gastric mucosa
A recently conducted meta-analysis revealed that H. pylori infection is the central reason for the growth of gastric cancer and affects males more aggressively than females [22]
H. pylori-induced chronic active gastritis has been associated with the initiation of intestinal type of gastric adenocarcinoma
Summary
Gastric cancer arises as a consequence of series of genetic, epigenetic and metabolic alteration in the mucus-producing cells on the inner surface of the gastric mucosa. Gastric cancer cells express a plethora of growth factor and cytokine receptor systems that form a highly complex interaction network between cancer cells and stromal cells within tumor microenvironment and impart. Gram-negative bacterium Helicobacter pylori successfully reside in the gastric mucosa and damages gastric epithelial cells [2]. H. pylori protect itself from acidic pH by epithelial secretions of bicarbonate buffer system and urea and the ammonia created by urease action and by tight attachment to mucosal glycan receptors [3]. Short-term colonization of H. pylori in gastric mucosa is asymptomatic [4], approximately 10% of H. pylori-infected individuals develop peptic ulcers, 1 to 3% develop gastric adenocarcinoma and
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