Gene expression profiling of inflammatory cytokines in esophageal biopsies of different phenotypes of gastroesophageal reflux disease: a cross-sectional study

Abstract

Background The clinical endoscopic phenotypes of gastroesophageal reflux disease (GERD) are classified as Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD is subclassified as abnormal acid exposure (AAE) and normal acid exposure (NAE) based on pH monitoring study results. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD. Methods This is an observational and cross-sectional study. All patients with BE, EE, AAE, and NAE and a control group were subjected to superior endoscopy (with biopsies of esophageal mucosa). Relative mRNA quantification of cytokine and target genes was conducted by quantitative Polymerase Chain Reaction (RT-qPCR). Changes in the expression of genes associated with inflammation were assessed for each disease phenotype. Statistical analysis of differential gene expression was performed using the Mann–Whitney U non-parametric test. A p value < 0.05 was considered significant. Results A total of 82 patients were included and were divided into the following groups: Group BE, 16 (19.51%); Group EE, 23 (28.04%); Group AAE, 13 (15.86%); NAE 13 (15.86%); and Control Group, 17 (20.73%). Compared with the control group, patients with BE exhibited increased IL-8 expression (p < 0.05) and increased levels of IL-10, MMP-3, and MMP-9. Patients with EE exhibited increased levels of IL-1B, IL-6 and IL-10 (p < 0.05), and patients with AAE exhibited increased expression of IL-1B, IL-6, IFN-γ and TNF-α (p < 0.05). AAE exhibited increased IL-1B and TNF-α expression compared with NAE (p < 0.05). Conclusion This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients with different GERD endoscopic phenotypes. IL-1B and TNF-α could be useful to differentially diagnose AAE and NAE in the non-erosive phenotype using endoscopic biopsies.

Local inflammatory response to gastroesophageal reflux: Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data

“…Unfortunately, in the mentioned study diagnosis of GERD was based predominantly on symptoms and endoscopy and did not include esophageal impedance monitoring. Similar to our results, they failed to reveal association of IL-10 expression with acid exposure in the esophagus[ 19 ]. This cytokine plays an anti-inflammatory and modulatory effect on inflammation and reduces production of TNFA , IL-1β , IL-12 , and secretion of interferon gamma[ 20 ].…”

“…According to the results, acid exposure time (proportion of time with pH < 4.0 per day at 5 cm above upper border of gastroesophageal sphincter) and, to a lesser extent, mean esophageal pH were the factors associated with gene expression of inflammatory cytokines. Zavala-Solares et al [ 19 ] succeeded in showing that the expression of IL-1β and TNFA were higher when an abnormal acid exposure in the esophagus (pH < 4 more than 4.2% of time per day) was present. Unfortunately, in the mentioned study diagnosis of GERD was based predominantly on symptoms and endoscopy and did not include esophageal impedance monitoring.…”

Herbal Medicine Hewei Jiangni Decoction Is Noninferior to Oral Omeprazole for the Treatment of Nonerosive Gastroesophageal Reflux Disease: A Randomized, Double-Blind, and Double-Dummy Controlled Trail

“…Among them, TNF, IL6, and IL1B are inflammatory cytokines, which can not only damage the esophageal mucosal barrier function of the GERD mouse [30][31][32] but activate acid-sensitive receptors on afferent nerves and epithelial cells of the esophageal mucosa, stimulating neurogenic inflammation and pain, leading to DIS and further increase in epithelial barrier permeability [33]. In addition, through endoscopic biopsy, IL-1B and TNF-α may help distinguish AAE and NAE in NERD [34]. MMP9 expresses in esophageal tissue of GERD patients, and is most common in severe forms compared to the mild forms [35].…”

Network Pharmacology Analysis of Hewei Jiangni Granule for Gastroesophageal Reflux Disease and Experimental Verification of Its Anti-Neurogenic Inflammation Mechanism

“…Moreover, abnormal acid exposure (AAE) exhibited obviously increased IL-1β and TNF-α expression compared with normal acid exposure. 36 Although PI3K-Akt and MAPK signaling pathway had higher P value in GO and KEGG enrichment analysis, progress of inflammatory reaction and nerve tissue conduction, which could be regulated by the HWJNG, were selected for experimental validation. This is more specific and in line with current research hotspots.…”