High Expression Of IL-18 Research Articles

Analysis of local expression of inflammatory cytokines genes in patients with gastroesophageal reflux disease and its association with types and number of gastroesophageal refluxes

The aim of the study was to evaluate gene expression of proinflammatory cytokines in esophageal mucosa in patients with erosive esophagitis (EE) and non-erosive form (NERD) of gastroesophageal reflux disease (GERD) and perform correlation analysis between the genes expression and types and number of gastroesophageal refluxes. Methods. This was a single-center prospective study. Esophageal mucosa samples were taken from lower part of the esophagus during endoscopy. Expression of IL-1b, IL-10, IL-18, TNFA, TLR4, GATA3, CD68 and beta-2 macroglobulin genes was assessed with ImmunoQuantex assays. Multichannel intraluminal esophageal pH-impedance studies were performed with Ohmega recorder and 2pH-6impedance catheters. Results. Data of 60 patients (females - 34; mean age (M±SD) 54.6 years, 20 - with erosive esophagitis) were available for the analysis. In those with EE, there was higher expression of IL-18 (5.89±0.4 vs 5.28±1.1, p=0.04), GATA3 (2.92±0.86 vs 2.23±0.96, p=0.03) genes, and inflammatory index (92.12±32.41% vs 70.1±30.8%, p=0.02) compared to NERD. Direct correlation was found between acid exposure time and expression of IL-1b (Spearman rank R = 0.29), IL-18 (R=0.31), TNFA (R=0.35), GATA3 (R=0.34), TLR4 (R=0.29), CD68 (R=0.37) genes and inflammatory index (R=0.3). Indirect correlation was revealed between mean рН and expressions of IL-18 (R= -0.28), TNFA (R= -0.33), GATA3 (R= -0.28), TLR4 (R= -0.28), CD68 (R= -0.39) genes and inflammatory index (R= -0.17). No correlation was found between the genes’ expression and number of gastroesophageal refluxes. Conclusions: Expression of proinflammatory cytokines’ genes differ in patients with EE and NERD. There is a correlation between expression of studied genes and esophageal acidity.

149. LOCAL INFLAMMATORY RESPONSE TO GASTROESOPHAGEAL REFLUX: ASSOCIATION OF GENE EXPRESSION OF INFLAMMATORY CYTOKINES WITH MULTICHANNEL INTRALUMINAL PH-IMPEDANCE DATA

Abstract Expression of inflammatory cytokines’ genes may take part in pathophysiology of different forms of gastroesophageal reflux disease (GERD). Aim: to explore the expression of inflammatory cytokines’ genes in esophageal mucosa in patients with erosive esophagitis and non-erosive forms of gastroesophageal reflux disease and its association with data of esophageal multichannel intraluminal pH-impedance measurements. This was a single-center prospective study. Esophageal mucosa samples were taken from lower part of the esophagus during endoscopy. Expression of IL-1β, IL-10, IL-18, TNFA, TLR4, GATA3, CD68, beta-2 macroglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays. Multichannel intraluminal esophageal pH-impedance (MII-pH) studies performed to all the participants. Diagnosis of GERD was confirmed by the results of MII-pH data. Patients were allocated to erosive esophagitis (EE) or non-erosive GERD groups (NERD). Non-symptomatic subjects with normal endoscopy and MII-pH results served as a control. Spearman rank correlation was used to asses association of genes expression and results of MII-pH. Data of 60 patients with GERD and 10 subjects of the control group were available for the analysis. Higher expression of IL-18 (5.89 ± 0.4 vs 5.28 ± 1.1, p = 0.04) and GATA3 (2.92 ± 0.86 vs 2.23 ± 0.96, p = 0.03) genes was found in EE group compared to NERD. Expression of IL-1β, IL-18, TNFA, and TLR4 genes was lower (P < 0.05) in the control group compared to EE and NERD. Esophageal acid exposure correlated with the expression of IL-1β (R = 0.29), IL-18 (R = 0.31), TNFA (R = 0.35), GATA3 (R = 0.34), TLR4 (R = 0.29), CD68 (R = 0.37) genes. Mean esophageal рН correlated inversely with the expressions of IL-18, TNFA, GATA3, TLR4, CD68 genes. In patients with erosive esophagitis, local expression of interleukin 18 and GATA3 transcription factor genes was higher compared to subjects with non-erosive form of gastroesophageal reflux disease. Esophageal acid exposure correlated directly with expression of IL-1β, IL-18, TNFA, TLR4, CD68 and B2M genes. Inverse correlation revealed between expression of IL-18, TNFA, GATA3, TLR4 CD68 genes and mean esophageal pH.

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

BACKGROUNDGene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease (GERD).AIMTo explore gene expression of inflammatory cytokines in esophageal mucosa in patients with erosive esophagitis (EE) and non-erosive forms of GERD (NERD) and its association with data of esophageal multichannel intraluminal impedance-pH (MII-pH) measurements.METHODSThis was a single-center prospective study. Esophageal mucosa samples were taken from the lower part of the esophagus during endoscopy. Expression of interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor α (TNFA), toll-like receptor 4 (TLR4), GATA binding protein 3 (GATA3), differentiation cluster 68 (CD68) and β-2 microglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays. MII-pH measurements were performed on all the participants. Diagnosis of GERD was confirmed by the results of the MII-pH data. Based on the endoscopy, patients were allocated to the groups of EE and NERD. The control group consisted of non-symptomatic subjects with normal endoscopy and MII-pH results. We used nonparametric statistics to compare the differences between the groups. Association of expression of the mentioned genes with the results of the MII-pH data was assessed with Spearman’s rank method.RESULTSData from 60 patients with GERD and 10 subjects of the control group were available for the analysis. Higher expression of IL-18 (5.89 ± 0.4 vs 5.28 ± 1.1, P = 0.04) and GATA3 (2.92 ± 0.86 vs 2.23 ± 0.96, P = 0.03) was found in the EE group compared to NERD. Expression of IL-1β, IL-18, TNFA, and TLR4 was lower (P < 0.05) in the control group compared to EE and NERD. Esophageal acid exposure correlated with the expression of IL-1β (Spearman’s rank r = 0.29), IL-18 (r = 0.31), TNFA (r = 0.35), GATA3 (r = 0.34), TLR4 (r = 0.29), and CD68 (r = 0.37). Mean esophageal рН correlated inversely with the expression of IL-18, TNFA, GATA3, TLR4, and CD68. No association of gene expression with the number of gastroesophageal refluxes was found.CONCLUSIONIn patients with EE, local expression of IL-18 and GATA3 was higher compared to subjects with NERD. Esophageal acid exposure correlated directly with expression of IL-1β, IL-18, TNFA, TLR4, CD68, and β-2 microglobulin genes. Inverse correlation was revealed between expression of IL-18, TNFA, GATA3, TLR4, and CD68 and mean esophageal pH.

Pin1 promotes pancreatic cancer progression and metastasis by activation of NF-κB-IL-18 feedback loop.

ObjectivesAccumulated evidence suggests that Pin1 contributes to oncogenesis of diverse cancers. However, the underlying mechanism of oncogenic function of Pin1 in PDAC requires further exploration. Materials and MethodsIHC was performed using PDAC tissues. Western blot, PCR, immunofluorescence and transwell were performed using cell lines. GSEA were applied for possible downstream pathways. ChIP assay and dual luciferase were used for assessment of transcriptional activity.ResultsBoth Pin1 and IL‐18 levels are increased in primary PDAC tissues and that their levels are positively correlated. High expression of IL‐18 is a predictor of poor prognoses. Pin1 promoted pancreatic cancer cell proliferation and motility by increasing IL‐18 expression, while Pin1 knockdown also inhibited the tumour‐promoting effect of IL‐18. Both Pin1 and IL‐18 could enhance the NFκB activity in pancreatic cancer cells. When bound to the p65 protein, Pin1 promoted p65 phosphorylation and its nuclear translocation. In the nucleus, Pin1 and p65 simultaneously bound to the IL‐18 promoter and enhanced IL‐18 transcription. In addition, recruitment of p65 to the IL‐18 promoter was decreased in Pin1‐silenced cells.ConclusionsOur study improves the understanding of Pin1 in tumour‐promoting inflammation in PDAC, which is a hallmark of cancer; Pin1 interacted with p65 in PDAC and enhanced NF‐κB signalling and downstream transcriptional activation of IL‐18, with increased IL‐18 continuously activating NF‐κB signalling, which then forms a positive feedback loop.

Short-lived AIM2 Inflammasome Activation Relates to Chronic MCMV Infection in BALB/c Mice.

Absent in melanoma 2 (AIM2) inflammasome is a crucial link bridging the innate host defense and the subsequent adaptive immunity when activated by exogenous double stranded DNA (dsDNA). Through establishing models of disseminated murine cytomegalovirus (MCMV) infection in BALB/c and C57BL/6 mice, we evaluated dynamic expression of AIM2 inflammasome components and its relationship with pathological damage and viral replication, trying to figure out whether AIM2 inflammasome is related to the chronic mechanism of MCMV. BALB/c and C57BL/6 mice were sacrificed on day 0, 1, 3, 7, 14 and 28 post infection. Expression levels of AIM2, pro-caspase-1, caspase-1 p20, pro-IL1β and mature IL1β in primary peritoneal macrophages (PMs) and spleens were detected by Western blotting. Contents of IL18 in the serum were detected by ELISA. Pathological examinations of livers were performed, and mRNA levels of MCMV glycoprotein B (gB) in salivary glands also assessed. Results showed that expression levels of AIM2 in PMs and spleens of C57BL/6 mice increased on day 3, even continued to day 28; caspase-1 p20 and mature IL1β increased on day 7, 14 and 28; the persistently high expression of IL18 in the serum started on day 1, showing a double peak curve. As for BALB/c mice, expression of AIM2 in PMs increased on day 1 and day 7, while contents of AIM2 in spleens increased on day 1 and day 3; caspase-1 p20 and mature IL1β merely increased 7 days fter infection. Thereafter, expression levels of AIM2, caspase-1 p20, mature IL1β and IL18 were limited; the duration of AIM2 inflammasome activation in BALB/c mice was much shorter than that in C57BL/6 mice. The severer pathological damage and more viral replications in BALB/c mice further proved the deficient antiviral immunity to MCMV. In conclusion, the activation of AIM2 inflammasome in BALB/c mice was short-lived, which is quite possibly related to the chronicity of MCMV infection.

The circulating level of interleukins 6 and 18 in ischemic and idiopathic dilated cardiomyopathy.

Introduction: By aging population, the heart failure and its life-threatening complications have become an enormous issue in public health. Regarding the inflammation as a major contributing pathological factor, the determination of most important inflammatory targets for immunomodulation is a problematic puzzle in the treatment of heart failure patients and the inflammatory pathways primarily involved in different underlying conditions contributing to heart failure can be an area which is worthy of focused research. Considering the dilated cardiomyopathy (DCM) as a relatively high-incident disease leading to heart failure, the aim of this study is to determine the difference in the expression level of interleukin (IL)-6 and IL-18 in patients with ischemic and idiopathic DCM. Methods: 39 non-diabetic patients with ischemic and 37 ones with idiopathic DCM were enrolled in the study. 48 healthy individuals were also considered as control group. For quantitative determination of the mRNA expression level of IL-6 and IL-18 genes, an in-house- SYBR Green real-time PCR was used and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was considered as internal control gene. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) was calculated by 2D echocardiographic assessment. Data were finally analyzed via SPSS statistical software version 19.0 using independent t test and 2-∆∆Ct method and P<0.05 were considered statistically significant. Results: The IL-6 was significantly higher expressed in patients with ischemic and idiopathic DCM than in healthy controls (274.3 and 168.8 times, respectively, both P values <0.001). The same higher expression of IL-18 was observed in ischemic DCM (48.5 times) and idiopathic DCM (45.2 times) compared with healthy individuals (both P values <0.001). Conclusion: Both ischemic and idiopathic DCM associates with IL-6 and IL-18 overexpression. However, no significant difference was observed between these two subtypes of DCM in either interleukin expression level. There is certainly need to further studies for evaluating the uniformity of results and also assessing other molecules in determining their roles in pathophysiology and probable utility for management.

A Functional Polymorphism inIL-18Is Associated with Severity of Bronchial Asthma

IL-18 is a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses. Recent murine and human genetic studies have shown its role in the pathogenesis of asthma. We conducted an association study in a Japanese population to discover variants of IL-18 that might have an effect on asthma susceptibility and/or progression and conducted functional analyses of the related variants. The IL-18 gene locus was resequenced in 48 human chromosomes. Asthma severity was determined according to the 2002 Global Initiative for Asthma Guidelines. Association and haplotype analyses were performed using 1,172 subjects. Although no polymorphisms differed significantly in frequency between the control and adult asthma groups, rs5744247 C>G was significantly associated with the severity of adult asthma (steps 1, 2 vs. steps 3, 4; P = 0.0034). We also found a positive association with a haplotype (P = 0.0026). By in vitro functional analyses, the rs5744247 variant was found to increase enhancer-reporter activity of the IL-18 gene in bronchial epithelial cells. Expression levels of IL-18 in response to LPS stimulation in monocytes were significantly greater in subjects homozygous for the susceptibility G allele at rs5744247 C>G. Furthermore, we found a significant correlation between the serum IL-18 level and the genotype of rs5744247 (P = 0.031). Although the association results need to be replicated by other studies, IL-18 variants are significantly associated with asthma severity, and the rs5744247 variant reflects higher transcriptional activity and higher expression of IL-18 in LPS-stimulated monocytes and a higher serum IL-18 level.