IL-10 Expression In Patients Research Articles

The impact of drug eluting stents on the co-release of interleukin-6 in patients with stable angina

Background: Drug-eluting stents represent an important revolution in the treatment of coronary artery disease. However, the mechanical trauma of stent deployment can trigger vascular injury and inflammatory cytokine cascades, potentially precipitating in-stent restenosis. The release of cytokines is not firmly established in patients with stable angina. Aims: To evaluate the acute effect of drug-eluting stents on the acute inflammatory response in patients with stable angina by quantifying interleukin-6 levels. Methods and materials: A single-centre exploratory study was conducted on 13 patients with stable angina undergoing elective angioplasty. Arterial blood samples were collected before angioplasty and directly after angioplasty. Additionally, venous blood samples were collected 24 hours post-angioplasty. Concentrations of interleukin-6 were analysed to assess changes in the acute inflammatory response. Results: IL-6 concentration significantly increased immediately after stent placement (5.95 ± 0.49 pg/ml, p = <0.05) and 24 hours post-stent placement (8.96 ± 1.16 pg/ml, p= <0.01). Gender-based analysis indicated significant increases in IL-6 levels in males post-stent placement (5.94 ± 0.08 pg/ml, p= < 0.05) and 24 hours post-stent placement (7.27 ± 0.56 pg/ml, p= < 0.01). Statin medication significantly reduced IL-6 expression in patients at baseline (3.27 ± 0.71 pg/ml versus 5.44 ± 0.18 pg/ml, p= < 0.05), but this distinction diminished rapidly after stent insertion, resulting in comparable IL-6 levels at 24 hours post-stent insertion in both groups. Conclusion: Interleukin-6 levels markedly increased immediately after coronary stenting, suggesting its role as an early initiator of the inflammatory response to coronary stenting. While limited by sample size, it lays the groundwork for larger, more comprehensive research to optimize drug-eluting stents outcomes and inflammatory management.

Determination of IL-6 Gene Promoter Polymorphism in Patients with Hepatitis C and Its Impact on RNA Secondary Structure.

Background and Objectives: A polymorphism in the promoter region of the IL-6 gene would influence the level of IL-6 expression in patients with HCV, resulting in a pro-inflammatory response. Few studies have shown the association between -174G>C (rs1800795) and -1363G>T (rs2069827) polymorphisms and HCV infection, and their results have been contradictory. There are no data published in our population to study such an IL-6 stimulus against HCV infection and its impact on RNA secondary structure. Therefore, we isolated human subjects from the province of Punjab, Pakistan. The objective was to screen for IL-6 gene promoter polymorphisms -174G/C and -1363G/T and those correlated with serum concentrations of IL-6 in patients with HCV and compared with a control. Materials and Methods: In conventional PCR, measurement of serum IL-6 by CLIA and statistical analysis were performed to observe the genotype association studies. By integrating bioinformatics and computational tools, our study aimed to provide a comprehensive understanding of how variations in the promoter region of IL-6 may have functional implications on gene expression. Results: The -174G>C and -1363G>T genotypes in the promoter region of patients with HCV were in strong allelic association (Δ = 0.97, p < 0.001). Interestingly, the bioinformatics analysis was well aligned with our experimental data. Conclusions: Based on the data, it can be inferred that IL-6 gene promoter polymorphisms are important in the dysregulation of IL-6 levels in patients with HCV.

Features of VEGF and IL-6 expression in patients with inflammatory breast cancer considering molecular-biological characteristics.

Expression of pro-malignant factors (VEGF) and cytokines like inflammatory components support breast cancer development. We examined 46 patients with stage IIIB inflammatory breast cancer (IBC) and 24 with stage IIA-IIIB breast cancer (BC) without secondary edema. Hormone receptors, Her-2/neu, Ki-67 index, VEGF, and IL-6, were determined for all patients before and after neoadjuvant treatment. They associated the expression of VEGF for IBC patients with an unfavorable prognosis. VEGF level for IBC lymph node metastases was higher than in patients without such lesions (1.4 times), and there was a significant increase in VEGF levels in the G3 category of malignancy (1.54-fold increase). In IBC patients with positive HER2/neu status, VEGF levels were 1.51 times higher compared to those with negative HER2/neu status (r=0.36, p<0.05). IL-6 level during therapy in IBC patients remained high, which occurs in active tumor development. Comparative analysis of the VEGF/IL-6 ratio during treatment of patients with IBC was higher vs. IIIB stage breast cancer without edema (1.4 vs. 0.7), indicating the aggressiveness of the tumor process and confirmed by an objective response to treatment (regression<30%).

LncRNA GAS5 positively regulates IL-10 expression in patients with generalized myasthenia gravis.

IntroductionLncRNA growth arrest‐specific transcript 5 (GAS5) has been proven to be involved in autoimmune diseases. Rheumatoid arthritis is a type of autoimmune disease that may affect myasthenia gravis (MG) patients. However, its direct role in MG is unknown.MethodsOur study included 62 generalized MG patients. GAS5 expression was analyzed with real‐time quantitative RT‐PCR (qRT‐PCR). The interaction between GAS5 and interleukin 10 (IL‐10) was explored in overexpressed cells using real time quantitative polymerase chain reactions (RT‐qPCRs) and western blot. The correlation of GAS5 and IL‐10 was analyzed using Pearson's correlation analysis. The diagnostic value of GAS5 for MG was analyzed using receiver operating characteristic (ROC) curve analysis.ResultsGAS5 and IL‐10 mRNA levels in peripheral blood mononuclear cells (PBMCs) were significantly lower in MG patients than healthy controls. Downregulated GAS5 effectively distinguished MG patients from healthy controls. GAS5 expression was positively correlated with IL‐10 expression in both MG patients and healthy controls. GAS5 overexpression significantly upregulated IL‐10 expression in PBMCs derived from both MG patients and healthy controls.ConclusionLncRNA GAS5 may improve generalized MG by positively regulating IL‐10 expression.

Genetic factors influence the survival rate of parotid salivary gland cancer patients

Introduction. The complex of transcriptional proteins of NF-kB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) family deservedly attracts attention as a factor capable of determining the course of malignant disease. Its promising study in combination with the expression of proinflammatory gene IL6 in patients with parotid cancer (PSG) is associated with the development of modulation of malignant disease treatment and risk assessment of the disease course. Aims — to determine the effect of the expression activity of the proinflammatory interleukin-6 gene and the NFKB1 transcriptional gene on the survival rate of patients with parotid cancer. Materials and methods. A cohort retrospective study was conducted in two groups. The epidemiological group of patients included 140 people from the cancer registry of Rostov region. The clinical part of the work was carried out on 25 patients with PSG cancer of both sexes aged 50 to 80 years. Followup period of the patients after radical surgery was 18 years. Expression activity of NFKB1 and IL6 genes was estimated by real-time PCR in tumor and conditionally healthy tissue. Patient survival rate was analyzed using Kaplan-Meier method. Results. According to the results of the survival analysis in the epidemiological group, the probability that an PSG cancer patient would survive the first year after diagnosis was 95.7%, three years — 82.4%, five years — 70.9% and 10 years — 31.2%. A comparative study of gene expression levels in tumor tissue samples compared to conditionally healthy tissue revealed an increase (p&lt;0.001) in the relative index for both the IL6 gene (5.7 times) and the NFKB1 gene (7.9 times).&gt;&lt;0.001) in the relative index for both the IL6 gene (5.7 times) and the NFKB1 gene (7.9 times). Discussion. Analysis of our data showed the possibility of using the complex evaluation of NFKB1 and IL6 gene expression in the cells of tumor samples of PSG cancer tissue obtained during surgery to predict the long-term survival of patients after surgical treatment. Conclusions. The expression profile of NFKB1 gene in tumor tissue was a proven prognostic factor determining the course of the disease in patients with PSG cancer, which should be taken into account when forming the prognosis of the disease. The expression of IL6 gene expression in tumor cells had no independent effect on the survival rate of PSG cancer patients, but contributed to the functional activation of NFKB1 transcription gene.

Dynamics of Plasmatic Levels of Pro- and Anti-Inflammatory Cytokines in HIV-Infected Individuals with M. tuberculosis Co-Infection.

Tuberculosis (TB) and HIV have profound effects on the immune system, which can lead to the activation of viral replication and negatively regulate the activation of T cells. Dysregulation in the production of cytokines necessary to fight HIV and M. tuberculosis may ultimately affect the results of the treatment and be important in the pathogenesis of HIV infection and TB. This work presents the results of a study of the expression of pro- and anti-inflammatory cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-1RA) in drug-naïve patients with dual infection of HIV/TB at the late stages of HIV-infection, with newly diagnosed HIV and TB, and previously untreated HIV in the process of receiving antiretroviral (ART) and TB treatment vs. a cohort of patients with HIV monoinfection and TB monoinfection. The study revealed that during a double HIV/TB infection, both Th1 and Th2 immune responses are suppressed, and a prolonged dysregulation of the immune response and an increased severity of the disease in pulmonary/extrapulmonary tuberculosis is observed in HIV/TB co-infection. Moreover, it was revealed that a double HIV/TB infection is characterized by delayed and incomplete recovery of immune activity. High levels of IL-6 were detected in patients with HIV/TB co-infection before initiation of dual therapy (2.1-fold increase vs. HIV), which persisted even after 6 months of treatment (8.96-fold increase vs. HIV), unlike other cytokines. The persistent enhanced expression of IL-6 in patients with dual HIV/TB co-infection allows the consideration of it as a potential marker of early detection of M. tuberculosis infection in HIV-infected individuals. The results of multivariate regression analysis showed a statistical trend towards an increase in the incidence of IRIS in patients with high IL-1Ra levels (in the range of 1550–2500 pg/mL): OR = 4.3 (95%CI 3.7–14.12, p = 0.53), which also allows IL-1Ra to be considered as a potential predictive biomarker of the development of TB-IRIS and treatment outcomes.

Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients.

Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19.Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile.Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay.Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels.Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention.Clinical Trial Registration: ClinicalTrials.gov identifier NCT04343053.

Adiponectin antagonises LPS-regulated secretion of inflammatory factors in airway epithelial cells, and its expression is regulated by many factors.

Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin and IL-6 expression in patients with acute exacerbation of COPD (AECOPD) was detected by ELISA. Human bronchial epithelial cells (HBECs) were stimulated with TNF-α, IL-6, apoptotic cells or LPS. Then, the expression of adiponectin was detected by qRT-PCR and western blotting, and pro- and anti-inflammatory factors were detected by ELISA. Adiponectin expression in AECOPD patients increased after treatment. TNF-α and apoptotic cells promoted adiponectin expression in HBECs in a dose-dependent manner, and apoptotic cells significantly promoted adiponectin secretion. IL-6 also promoted adiponectin expression, but it inhibited adiponectin expression at high doses and with long treatment times. LPS inhibited adiponectin expression, but when HBECs were pretreated with anti-TNF-α and then treated with LPS, the expression and secretion of adiponectin increased significantly with increasing anti-TNF-α concentrations. Adiponectin stimulated the secretion of pro-inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti-inflammatory factors in a dose-dependent manner. Although LPS also stimulated HBECs to secrete pro-inflammatory and anti-inflammatory factors, adiponectin inhibited LPS-induced pro-inflammatory factor secretion and enhanced anti-inflammatory factor secretion. Many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation. SIGNIFICANCE OF THE STUDY: Many studies have shown that adiponectin is closely related to chronic obstructive pulmonary disease (COPD), but the specific role of adiponectin in COPD is still not well understood. Adiponectin expression in AECOPD patients increased after treatment. TNF-α, IL-6 and apoptotic cells promoted adiponectin expression in HBECs. Adiponectin stimulated the secretion of pro-inflammatory factors in HBECs, but this effect was not concentration dependent. Adiponectin promoted the secretion of anti-inflammatory factors in a dose-dependent manner. Adiponectin inhibited LPS-induced pro-inflammatory factor secretion and enhanced anti-inflammatory factor secretion. Therefore, many factors regulate the expression and secretion of adiponectin, and adiponectin regulates the balance of the inflammatory response and inhibits further expansion of inflammation.

Abstract B16: The immune profile of sentinel lymph nodes in melanoma

Abstract Background: Immune cell composition and immune-mediated processes occurring in the sentinel lymph node (SLN) of melanoma patients regulate generation of tumor-specific effector T-cell responses and ultimately tumor control. We hypothesized that comprehensive analysis of these immune-associated processes in the SLN biopsy may identify patients at high risk of melanoma recurrence. Methods: We analyzed 38 formalin-fixed, paraffin-embedded sentinel lymph nodes from melanoma patients undergoing SLN biopsy from 2009-2012 using the NanoString nCounter® PanCancer Immune Profiling panel. The panel included 770 immune related genes. Results: Of 38 patients, 19 were SLN negative and 19 were SLN positive. Among SLN-negative patients (n=19), the median Breslow depth was 1.25 mm, and 21% (n=4) had developed recurrence at median follow-up of 6.2 years. Among SLN-positive patients, the median Breslow depth was 3.35 mm and 37% (n=7) had developed recurrence at median follow-up of 6.5 years. There were 31 genes significantly differentially expressed (P&amp;lt;0.01) in SLN positive compared to SLN negative, including higher relative expression of B-cell signaling markers (CD19, CD22, Pax5, CXCR5, CD79B). Among all 38 patients, there were 13 genes differentially expressed (P&amp;lt;0.05) between patients with and without recurrence, including higher relative expression of IL6 in patients with recurrence compared to no recurrence. Further analysis is ongoing. Conclusion: In this retrospective series, we found the immunologic gene expression profile of melanoma SLNs was significantly different in SLN negative versus SLN positive. There were also significant differences in the profile between patients who developed melanoma recurrence versus no recurrence regardless of SLN status. We aim to build on these pilot data. The goal is to use this profile to predict patients at high risk of recurrence after SLNB who may benefit from adjuvant therapy. Citation Format: Georgia M. Beasley, Eda K. Holl, Norma E. Farrow, Margaret G. Leddy, April K. Salama, Brent A. Hanks, Smita K. Nair. The immune profile of sentinel lymph nodes in melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B16.

Identification of Hub genes associated with infection of three lung cell lines by SARS-CoV-2 with integrated bioinformatics analysis.

Identification of Hub genes associated with infection of three lung cell lines by SARS-CoV-2 with integrated bioinformatics analysis.

Comparison of Efficacy between Clopidogrel and Ticagrelor in Patients with Acute Coronary Syndrome after Interventional Treatment and Their Effects on IL-6

We aimed to compare the efficacy between clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) and their effects on IL-6. A retrospective analysis and collection of 200 ACS patients diagnosed by the Department of Cardiology, Affiliated Hospital of Qingdao University, Qingdao, China in 2016 were performed. Patients were randomly divided into clopidogrel group and ticagrelor group. Data of left ventricular ejection fraction and ACS clinical classification before PCI, PCI treatment, IL-6, platelet aggregation status, maximum platelet aggregation rate (MPAR), P2Y12 response unit (PRU) and adverse reaction of patients were collected. After PCI, patients were followed up for 1 year to compare the ischemia after treatment between clopidogrel group and tigravilol group. MPAR and PRU after PCI of clopidogrel group were significantly higher than those of ticagrelor group (P<0.05). The expression of IL-6 in two groups peaked at 1 day after PCI and then decreased. That of ticagrelor group was consistently lower than that of clopidogrel group (P<0.05). The incidence of ischemic events after treatment in clopidogrel group was significantly higher than that in ticagrelor group (P<0.001). Compared with clopidogrel, tigerrilol had more significant inhibition of platelet aggregation after PCI in ACS patients, and tigerrilol had better effect after interventional treatment in ACS patients. In addition, compared with clopidogrel, tegrel can significantly inhibit the expression of IL-6 in patients with ACS and better alleviate the inflammatory response after PCI.

MicroRNA-365 regulates the occurrence and immune response of sepsis following multiple trauma via interleukin-6.

In the present study, the expression of microRNA (miR)-365 and interleukin (IL)-6 in peripheral blood mononuclear cells and serum from patients with sepsis following multiple trauma has been investigated. A total of 26 patients with sepsis following multiple trauma were included as the experimental group, whereas 21 contemporaneous patients without sepsis following multiple trauma were included as the negative control group. The expression of IL-6 mRNA and miR-365 was determined by reverse transcription-quantitative polymerase chain reaction, and western blot analysis was used to measure IL-6 protein expression. ELISA was performed to determine the secretion of IL-6 protein. Following stimulation with lipopolysaccharide (LPS) for 24 h, THP-1 cells were used to examine the expression of miR-365 and the levels of IL-6 protein and mRNA in cells simulating sepsis. A dual luciferase reporter assay revealed that IL-6 mRNA was a direct target of miR-365. Patients with sepsis following multiple trauma exhibited significantly higher IL-6 mRNA and protein levels than patients without sepsis (P<0.05). In addition, miR-365 expression in patients with sepsis following trauma was significantly lower than in patients without sepsis (P<0.05). Similar effects were observed in THP-1 cells treated with LPS. The present study demonstrated that increased expression of IL-6 in patients with sepsis following multiple trauma is associated with decreased expression of miR-365. miR-365 may regulate the occurrence and immune response of sepsis following multiple trauma via IL-6. These results may elucidate agents for clinical diagnosis and treatment of the disease.

Lung injury caused by paraquat poisoning results in increased interleukin-6 and decreased microRNA-146a levels.

The aim of the present study was to investigate the expression of microRNA (miR)-146a in the pulmonary macrophages, peripheral blood mononuclear cells and serum of patients with lung injury caused by paraquat poisoning, as well as the underlying mechanism of its regulation in the disease. A total of 26 patients with lung injury caused by paraquat poisoning were included in the present study. In addition, 33 healthy subjects were included as the control group. The expression levels of interleukin (IL)-6 mRNA and miR-146a was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blotting was used to measure IL-6 protein expression, while enzyme-linked immunosorbent assay was also performed to determine the secretion of IL-6 protein. A dual-luciferase reporter assay was conducted to examine whether IL-6 mRNA is a direct target of miR-146a. Patients with lung injury caused by paraquat poisoning exhibited higher IL-6 mRNA and protein levels as compared with those in healthy subjects. In addition, miR-146a expression in patients with paraquat poisoning-induced lung injury was significantly reduced in comparison with that in healthy subjects. Notably, the overexpression of miR-146a by mimic transfection downregulated the expression of IL-6 in pulmonary macrophages. The results of dual-luciferase reporter assay demonstrated that IL-6 mRNA was a direct target of miR-146a. Therefore, the present study demonstrated that increased expression of IL-6 in patients with lung injury caused by paraquat poisoning is associated with decreased expression of miR-146a. Furthermore, miR-146a may regulate the occurrence and immune response of lung injury caused by paraquat poisoning and this process is possibly achieved via IL-6, an important cytokine that mediates inflammation.

Intestinal IFN-γ–producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease

IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (TR1) cells but is also produced by CD25+ regulatory T (Treg) cells. We aimed to identify and characterize human intestinal TR1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs). CD4+ T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities. Intracellular IL-10 expression by CD4+ T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1β and IL-23 responsiveness was assessed. Intestinal TR1 cells could be identified by coexpression of CCR5 and programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5+PD-1+ TR1 cells expressed IFN-γ and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-γ+ TR1 cells, but not IL-7 receptor-positive TH cells or CD25+ Treg cells, showed lower IL-10 expression in patients with IBDs. TR1 cells were responsive to IL-23, and IFN-γ+ TR1 cells downregulated IL-10 with IL-1β and IL-23. Conversely, CD25+ Treg cells expressed higher levels of IL-1 receptor but showed stable IL-10 expression. We provide the first exvivo characterization of human intestinal TR1 cells. Selective downregulation of IL-10 by IFN-γ+ TR1 cells in response to proinflammatory cytokines is likely to drive excessive intestinal inflammation in patients with IBDs.

Social isolation impairs remyelination in mice through modulation of IL-6.

Recent studies have revealed that social experience affects myelination. These findings have important implications for disorders that feature abnormal myelination, such as multiple sclerosis (MS), as previous studies have shown that psychosocial stress exacerbates the pathobiology of MS. However, most studies have focused on psychosocial stress during the demyelination phase of MS and have not investigated the effects of social experience on remyelination. Thus, the current study sought to determine whether social experience can alter remyelination after myelin depletion. Myelin in the mouse medial prefrontal cortex was depleted with cuprizone, and the effects of subsequent social isolation on remyelination were evaluated. Remyelination was severely impaired in socially isolated mice. Social isolation also increased IL-6 levels in the medial prefrontal cortex, and administration of an IL-6 inhibitor (ND50 = 0.01-0.03 μg for 0.25 ng/ml IL-6) ameliorated remyelination impairments. Consistent with this result, IL-6 administration (ED50 = 0.02-0.06 ng/ml) disturbed remyelination. In addition, neuron-oligodendrocyte coculture experiments showed that IL-6 treatment (ED50 ≤ 0.02 ng/ml) markedly impeded myelination, which was recovered with IL-6 inhibitor administration (ND50 = 0.01-0.03 μg for 0.25 ng/ml IL-6). This study provides the first direct evidence, to our knowledge, that social experience influences remyelination via modulation of IL-6 expression. These findings indicate that psychosocial stress may disturb remyelination through regulation of IL-6 expression in patients with such demyelinating diseases that involve remyelination as MS.-Makinodan, M., Ikawa, D., Miyamoto, Y., Yamauchi, J., Yamamuro, K., Yamashita, Y., Toritsuka, M., Kimoto, S., Okumura, K., Yamauchi, T., Fukami, S., Yoshino, H., Wanaka, A., Kishimoto, T. Social isolation impairs remyelination in mice through modulation of IL-6.

SAT0036 Tumor necrosis factor-alpha co-activated T-cells support a profibrotic cytokine milieu on cost of IL-10 expression in patients with systemic sclerosis

BackgroundLow grade inflammation is an increasingly recognized feature in patients suffering from systemic sclerosis (SSc), with substantial infiltration and activation of lymphocytes occurring in SSc affected tissue. However, the transition...

Abstract 4194: The hereditary genetic polymorphism of mir-608 predicts the clinical outcome and expression of IL-6 in patients with esophageal squamous cell carcinoma .

Abstract PURPOSE: To investigate the effect of the single nucleotide polymorphisms (SNPs) in microRNA-related genes on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: A total of 504 patients with a diagnosis of ESCC were enrolled in the study. The genotypes of miRNA-related SNPs were analyzed from the genomic DNA of peripheral leukocytes and were correlated with the clinical outcome of patients, which was first evaluated in a randomly assigned training set (n=129) and subsequently verified by a replication set (n= 375). RESULTS: In training group, the heterozygous CG genotype of mir-608 rs4919510 was associated with reduced risk for adverse clinical outcomes (HR [95% CI] =0.47 [0.27-0.82] for death; HR [95% CI] =0.47 [0.29-0.77] for recurrence). In contrast, both homozygous CC and GG genotypes showed unfavorable for prognosis. The associations were confirmed in an independent replication group (GG+CC vs. CG, HR [95% CI] =1.36 [1.07-1.73], P=0.013 for death; HR [95% CI] = 1.26 [1.00-1.59], P=0.048 for recurrence). The prognostic effect was more pronounced among patients with advanced tumor stages and in those treated with concurrent neoadjuvant chemo- radiotherapy (CCRT). Functional relevance of rs4919510 was correlated with the serum IL-6 levels. GG variant was significantly associated with IL-6 over-expression in advanced ESCC patients. CONCLUSION: The hereditary genetic variants in mir-608 can serve as an independent predictor for the clinical outcome of ESCC patients. The prognostic effect of rs4919510 may be partially mediated by impairing the ability in regulating IL-6 expression. Citation Format: Pei-Wen Yang, Ching-Yueh Hsieh, Yu-Ting Huang, Ya-Chuan Huang, Tzu-Hsuan Chiang, Jang-Ming Lee. The hereditary genetic polymorphism of mir-608 predicts the clinical outcome and expression of IL-6 in patients with esophageal squamous cell carcinoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4194. doi:10.1158/1538-7445.AM2013-4194

Association of Promyelocytic Leukemia Protein with Expression of IL-6 and Resistance to Treatment in Multiple Myeloma

Background/Aims: Promyelocytic leukemia protein (PML) was originally identified as a tumor suppressor but has been recently shown to have the ability to control stem cell function in multiple tissues including malignancies. This study aimed to evaluate the biological and clinical significance of PML in multiple myeloma (MM). Methods: We knocked down PML in myeloma cells with a lentiviral vector expressing microRNA to target PML, which were used for in vitro analyses. We also evaluated the association between PML expression in the bone marrow and patients’ clinical parameters. Results: The expression of IL-6 was decreased in myeloma cells with knocked-down PML expression. Immunohistochemical study showed that the PML expression level varied widely in the bone marrow of 48 MM patients, and that IL-6 expression correlated with PML expression in these patients. In addition, MM with high PML expression at diagnosis showed a poor prognosis regarding the 2-year survival, and PML and IL-6 positivity increased with the progression of disease in 13 sequentially analyzed cases. Conclusions: These results suggest that PML expression was positively associated with IL-6 expression in patients and was also related to tumor development and resistance to treatment in MM.

Altered HLA Class I and HLA-G Expression Is Associated with IL-10 Expression in Patients with Cervical Cancer

Although high-risk human papillomaviruses (HPVs) are an important risk factor in the etiopathogenesis of cervical cancer, increasing evidence suggests that the ability to avoid immune surveillance seems to be linked to the transforming potential of HPV and a rapid progression to cancer. In other cancer models, IL-10 contributes to impair anti-tumor immune response either by downregulating human leukocyte antigen Class I (HLA-I) expression or by increasing HLA-G expression. To comprehend how these alterations could contribute to evasion of immune surveillance in cervical cancer, we analyzed HLA-I, HLA-G and IL-10 expressions by immunohistochemistry in 63 biopsies from patients with cervical intraepithelial neoplasia III (CIN-III) and cervical cancer. Immunohistochemistry showed absent or weak HLA-I expression in 50/59 cases. In these cases, a high percentage had loss of heterozygosis. IL-10 and HLA-G expression were observed in 46.6 and 27.6% of cases, respectively. Concurrent upregulation of IL-10 was found in 87.5% of HLA-G positive cases (p = 0.000). Similarly, a significant association between IL-10 expression and HLA-I downregulation was found (p = 0.028). Finally, we observed higher HLA-G expression in patients with HLA-I downregulation than in those with normal HLA-I expression (p = 0.004). Our results suggest that, in cervical cancer, the IL-10 expression may induce an immunosuppressive environment by upregulating HLA-G expression and downregulating HLA class I expression.

Activation and Overexpression of PARP-1 in Circulating Mononuclear Cells Promote TNF-α and IL-6 Expression in Patients with Unstable Angina

Proinflammatory cytokines are involved in the development of unstable angina (UA). Poly(ADP-ribose) polymerase-1 (PARP-1) contributes importantly to regulating the transcription of inflammatory cytokines. This study aims to investigate the relationship of PARP-1 in circulating mononuclear cells (MNCs) and plasma TNF-alpha and IL-6 in UA patients and to elucidate the mechanism that PARP-1 promotes TNF-alpha and IL-6 expression via NF-kappaB pathway. Twenty six Braunwald class IIIB UA patients, 25 stable angina patients and 25 healthy volunteers were enrolled in this study. Plasma TNF-alpha and IL-6 were determined with ELISA. Circulating MNCs were analyzed for PARP activity, PARP-1 expression and NF-kappaB DNA binding activity. MNCs from healthy subjects were cultured to investigate the direct effects of PARP-1 on NF-kappaB DNA binding activity and the expression of TNF-alpha and IL-6. PARP activity and PARP-1 expression in circulating MNCs were increased and positively correlated with plasma TNF-alpha and IL-6, respectively, in UA patients. Spontaneous NF-kappaB activation in MNCs was demonstrated in UA patients. In cultured MNCs from healthy subjects, inhibition of PARP-1 prevented lipopolysaccharide-induced increase in DNA binding activity of NF-kappaB and the expression of TNF-alpha and IL-6. Supershift assay demonstrated that PARP-1 was a component of NF-kappaB/DNA complex. Addition of recombinant human PARP-1 protein to nuclear extracts of MNCs significantly increased the DNA binding activity of NF-kappaB. Activation and overexpression of PARP-1 are demonstrated in circulating MNCs of UA patients. Overexpressed PARP-1 promotes PARP-1/NF-kappaB/DNA complex formation, thereby enhancing the expression of TNF-alpha and IL-6 in circulating MNCs of UA patients.