Abstract
Helicobacter pylori (H. pylori) induces an intense inflammatory response, mediated by proinflammatory cytokines, including interleukin (IL)-6 and its membrane receptor (IL-6R), which activates important signaling pathways in the development of gastric disease and cancer. We investigated the gene and protein expression of IL-6 and IL-6R and the influence of polymorphisms rs1800795, rs1800796, and rs1800797 on its gene expression together with H. pylori infection. Furthermore, an in-silico analysis was performed to support our results. Gastric biopsies were obtained from patients with gastric symptoms and patients with gastric cancer (GC) and were divided into groups (Control, Gastritis, and Cancer). H. pylori was detected by PCR. Real-time-qPCR was employed to determine gene expression, and western blot assay was used to analyze protein expression levels. PCR-RFLP was used to characterize IL-6 polymorphisms. Bioinformatics analyses were performed using the Gene Expression Omnibus (GEO) database and GEO2R to screen out differentially expressed genes (DEGs). H. pylori was detected in 43.3% of the samples. Statistically significant differences were found for IL-6 (P=0.0001) and IL-6R (P=0.0005) genes among the three groups, regardless of the presence of H. pylori. Among patients with H. pylori infection, the IL-6 and IL-6R gene and protein expressions were significantly increased, highlighting IL-6 gene overexpression in patients with GC. No statistically significant differences were found for the rs1800795, rs1800796, and rs1800797 polymorphisms compared to IL-6 gene expression. The results indicated that the IL-6 polymorphisms do not influence its expression, but IL-6 and IL-6R expression seems to be altered by the presence of H. pylori.
Highlights
Since its first identification in 1983 by Robin Warren and Berry Marshal, Helicobacter pylori (H. pylori) has been associated with many gastric diseases, including gastric cancer (GC) [1]
H. pylori has been reported as the most common cause for the development of GC, since its colonization in the gastric mucosa leads to an intense inflammatory process, stimulating the transcription and production of proinflammatory molecules, such as interleukin 6 (IL-6)
H. pylori was detected in 43.3% of the samples analyzed, with a higher prevalence in the Gastritis and Cancer groups compared to the Control group, confirming that its presence increased the risk for the development of gastric diseases
Summary
Since its first identification in 1983 by Robin Warren and Berry Marshal, Helicobacter pylori (H. pylori) has been associated with many gastric diseases, including gastric cancer (GC) [1]. IL-6 is involved in the defense of the organism, functioning as a messenger between an innate and adaptive immune response, and the presence of H. pylori promotes an increase in its synthesis, contributing to inflammation and leading to gastritis [3,4]. The IL-6/IL-6R complex activates important signaling pathways in inflammatory and carcinogenic processes [6,7,8,9] When expressed, it may act as an anti-apoptotic factor in esophageal carcinoma cells by activating the STAT3 and JAK signaling pathway [7]. Taniguchi and Karin [10] showed that increased expression of IL-6 gene favored the invasion of cells from carcinoma in the esophagus. A significant association was observed between high expression of IL-6R gene and tumor invasions and metastases [7]
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