603-P: Circulating Inflammatory Cells and Inflammasome Activation in Diabetics with Diabetic Retinopathy (DR)

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 603-P
Author(s):  
MARIANA D. DUPONT ◽  
ANA LEDA LONGHINI ◽  
GOPALKRISHNA SREEJIT ◽  
RAM PRASAD ◽  
PRABHAKARA NAGAREDDY ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Inflammatory Cells ◽  
Inflammasome Activation

Polymorphisms of interleukin-4, -10 and 12B genes and diabetic retinopathy

2011 ◽  
Vol 6 (4) ◽  
pp. 558-564 ◽  
Author(s):  
Ines Cilenšek ◽  
Amela Hercegovac ◽  
Jovana Starčević ◽  
Katarina Vukojević ◽  
Mirna Babić ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Inflammatory Cells ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Interleukin 12 ◽  
Cross Sectional ◽  
Increased Risk ◽  
Promoter Gene

AbstractIn diabetic retinopathy (DR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells, and angiogenic factors are present. We investigated the hypothesis that rs2243250 polymorphism of the interleukin 4 (IL-4) gene or rs1800896 polymorphism of the interleukin 10 (IL-10) gene, and rs3212227 polymorphism of the 3’ untranslated region (3’ UTR) of the interleukin-12 p40 gene (IL12B) may be associated with the development of proliferative diabetic retinopathy (PDR) in Caucasians with type 2 diabetes (DM2). This cross sectional case — control study included 189 patients with PDR and 187 patients with type 2 diabetes without PDR. Polymorphisms rs1800896 of the IL-10 gene, rs2243250 of the IL-4 gene, and rs3212227 of IL12B gene were analyzed by ARMS -PCR and RFLP -PCR methods. Multivariate analysis demonstrated the GG genotype of the rs1800896 polymorphism of the IL-10 gene to be associated with increased risk for PDR (OR=1.99; 95% CI=1.11–3.57; P=0.02), whereas the TT genotype of the rs2243250 polymorphism of the IL-4 gene and the AA genotype of the rs3212227 polymorphism of the IL-12 gene were not independent risk factors for PDR. Our findings suggest that the genetic variations at the IL-10 promoter gene might be a genetic risk factor for PDR in Caucasians with type 2 diabetes.

scholarly journals Knockdown of KCNQ1OT1 Alleviates the Activation of NLRP3 Inflammasome Through miR-17-5p/TXNIP Axis in Retinal Müller Cells

2021 ◽  
Author(s):  
Yu Liu ◽  
Guoping Cao ◽  
Lili Dong ◽  
Lele Li ◽  
Yuping Dou ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Nlrp3 Inflammasome ◽  
Critical Role ◽  
Müller Cells ◽  
Clinical Samples ◽  
Inflammasome Activation ◽  
Muller Cells ◽  
Potential Mechanism ◽  
Nlrp3 Inflammasome Activation ◽  
Therapeutic Value

Abstract Diabetic retinopathy (DR) is one of the most severe and common complications caused by diabetic mellites. Inhibiting NLRP3 inflammasome activation displays a crucial therapeutic value in DR. Studies have shown that KCNQ1OT1 plays a critical role in regulating NLRP3 inflammasome activation and participates in the pathogenesis of diabetic complications. The present study aims to explore the role, and the potential mechanism of KCNQ1OT1 in regulating the activation of NLRP3 inflammasome in DR. The expression of KCNQ1OT1 and the activation of NLRP3 inflammasome were increased in experimental DR models. KCNQ1OT1 knockdown alleviated NLRP3 inflammasome-associated molecules expression. In addition, KCNQ1OT1 was found to be localized mainly in the cytoplasm of Müller cells and facilitated TXNIP expression by acting as a miR-17-5p sponge. KCNQ1OT1 promoted the activation of NLRP3 inflammasome through miR-17-5p/TXNIP axis. Moreover, the clinical samples of patients with DR showed that the expression of KCNQ1OT1 and the activation of NLRP3 inflammasome were all increased, further supporting the hypothesis that the KCNQ1OT1 dysregulation may be the molecular mechanism of the pathogenesis of DR. Therefore, KCNQ1OT1 may serve as a new therapeutic target for DR.

scholarly journals The Role of the Inflammasome in Heart Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Jimin Wu ◽  
Erdan Dong ◽  
Youyi Zhang ◽  
Han Xiao
Keyword(s):  
Heart Failure ◽  
Pressure Overload ◽  
Inflammatory Cells ◽  
Cardiac Cells ◽  
Current Evidence ◽  
Inflammasome Activation ◽  
Cardiac Inflammation ◽  
Promising Therapeutic Target ◽  
Multimeric Protein

Inflammation promotes the development of heart failure (HF). The inflammasome is a multimeric protein complex that plays an essential role in the innate immune response by triggering the cleavage and activation of the proinflammatory cytokines interleukins (IL)-1β and IL-18. Blocking IL-1β with the monoclonal antibody canakinumab reduced hospitalizations and mortality in HF patients, suggesting that the inflammasome is involved in HF pathogenesis. The inflammasome is activated under various pathologic conditions that contribute to the progression of HF, including pressure overload, acute or chronic overactivation of the sympathetic system, myocardial infarction, and diabetic cardiomyopathy. Inflammasome activation is responsible for cardiac hypertrophy, fibrosis, and pyroptosis. Besides inflammatory cells, the inflammasome in other cardiac cells initiates local inflammation through intercellular communication. Some inflammasome inhibitors are currently being investigated in clinical trials in patients with HF. The current evidence suggests that the inflammasome is a critical mediator of cardiac inflammation during HF and a promising therapeutic target. The present review summarizes the recent advances in both basic and clinical research on the role of the inflammasome in HF.

Abstract 127: Txnip-Mediated NLRP3 Inflammasome Activation as a Novel Mechanism of Myocardial Ischemia-Reperfusion Injury

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Yi Liu ◽  
Lijian Zhang ◽  
Yan Qu ◽  
Chao Gao ◽  
Jingyi Liu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Inflammasome Activation ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Myocardial Ischemia Reperfusion

As an inhibitor of the antioxidant thioredoxin, thioredoxin-interacting protein (Txnip) is linked to insulin resistance. NLRP3 inflammasome, a major regulator of innate immunity, has been reported to be activated by Txnip, thus contributing to the pathogenesis of type 2 diabetes mellitus. However, the role of Txnip and its NLRP3 inflammasome activation in the myocardial ischemia/reperfusion (MI/R) injury has not been previously investigated. C57BL/6J mice were subjected to 30 min of ischemia and 3 or 24 hrs of reperfusion. The ischemic heart exhibited increased Txnip and NLRP3 expressions, increased interaction between Txnip and NLRP3 (by immunoprecipitation, 1.8-fold increase over sham), and increased IL-1β, IL-18 and caspase-1 expressions (%increase: 80%, 77% and 110%, respectively) (n=8, all P <0.05). Compared with vehicle group, those mice either receiving intramyocardial small-interfering RNA (siRNA) injection to specifically knockdown the myocardial NLRP3 or intraperitoneal injection of the inflammasome inhibitor (BAY 11-7082) exhibited significantly improved cardiac function (by 28% and 25%), decreased the infarct size (by 40% and 38%), and decreased the cardiomyocytes apoptosis (all P <0.05). NLRP3 knockdown or inflammasome inhibitor also decreased the inflammatory cells infiltration (macrophages and neutrophils) and cytokines (TNF-α, INF-γ and IL-6) production (all P <0.05). To elucidate the role of Txnip in the NLRP3 activation in MI/R, intramyocardial injection of Txnip siRNA was performed to specifically knockdown the myocardial Txnip expression. Compared with vehicle, the Txnip knockdown significantly decreased Txnip/NLRP3 interaction and NLRP3activation as evidenced by lower expressions of IL-1β and caspase-1, decreased inflammatory cells infiltration and cytokines expressions, and consequently decreased the myocardial infarct size and increased the heart function (all P <0.05). Collectively, we demonstrated for the first time that Txnip mediatedNLRP3 inflammasome activation is a novel mechanism of MI/R injury. Interventions targeted to blocking the activation of NLRP3 by inhibiting Txnip may have therapeutic potential for preventing MI/R injury.

scholarly journals Tonabersat Inhibits Connexin43 Hemichannel Opening and Inflammasome Activation in an In Vitro Retinal Epithelial Cell Model of Diabetic Retinopathy

2020 ◽  
Vol 22 (1) ◽  
pp. 298
Author(s):  
Heather Lyon ◽  
Avik Shome ◽  
Ilva D. Rupenthal ◽  
Colin R. Green ◽  
Odunayo O. Mugisho
Keyword(s):  
Diabetic Retinopathy ◽  
Cell Model ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Inflammasome Activation ◽  
Cytokine Release ◽  
Caspase 1 ◽  
Release Assay ◽  
Connexin Hemichannel

This study was undertaken to evaluate the connexin hemichannel blocker tonabersat for the inhibition of inflammasome activation and use as a potential treatment for diabetic retinopathy. Human retinal pigment epithelial cells (ARPE-19) were stimulated with hyperglycemia and the inflammatory cytokines IL-1β and TNFα in order to mimic diabetic retinopathy molecular signs in vitro. Immunohistochemistry was used to evaluate the effect of tonabersat treatment on NLRP3, NLRP1, and cleaved caspase-1 expression and distribution. A Luminex cytokine release assay was performed to determine whether tonabersat affected proinflammatory cytokine release. NLRP1 was not activated in ARPE-19 cells, and IL-18 was not produced under disease conditions. However, NLRP3 and cleaved caspase-1 complex formation increased with hyperglycemia and cytokine challenge but was inhibited by tonabersat treatment. It also prevented the release of proinflammatory cytokines IL-1β, VEGF, and IL-6. Tonabersat therefore has the potential to reduce inflammasome-mediated inflammation in diabetic retinopathy.

scholarly journals A Flow Cytometric Analysis of Vitreous Inflammatory Cells in Patients with Proliferative Diabetic Retinopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Mojca Urbančič ◽  
Veronika Kloboves Prevodnik ◽  
Daniel Petrovič ◽  
Mojca Globočnik Petrovič
Keyword(s):  
Diabetic Retinopathy ◽  
T Lymphocytes ◽  
Proliferative Diabetic Retinopathy ◽  
Venous Blood ◽  
Flow Cytometric Analysis ◽  
Inflammatory Cells ◽  
Control Group ◽  
Tractional Retinal Detachment ◽  
Local Inflammatory Response ◽  
Flow Cytometric

The purpose of this study was to investigate inflammatory cells in vitreous from patients with proliferative diabetic retinopathy (PDR) using flow cytometric analysis. Twenty-eight patients with PDR requiring vitrectomy because of macular traction or tractional retinal detachment were enrolled in the study (n=28), and 6 patients with macular hole (MH) formed the control group. Samples of vitreous and peripheral venous blood were obtained at the beginning of vitrectomy. T lymphocytes were found in vitreous from patients with PDR, and CD4/CD8 ratio was higher in vitreous (median 4.3) compared to blood (median 1.9;P=0.003). No B lymphocytes were detected in vitreous. The percentage of histiocytes/macrophages was significantly higher in vitreous (median 62.1) in comparison with blood (median 5.5;P<0.0001). No lymphocytes were detected in vitreous of the control group. There were more T lymphocytes in vitreous from patients with active PDR. No association between cells in the vitreous and visual acuity improvement after surgery was found. In conclusion, T lymphocytes are found in vitreous from patients with PDR and reflect the activity of PDR but do not seem to predict visual prognosis. Higher CD4/CD8 ratio in vitreous compared to blood from patients with PDR is consistent with local inflammatory response in PDR.

scholarly journals Association between interleukin-10 gene rs1800896 polymorphism and diabetic retinopathy in a Chinese Han population

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Lun Liu ◽  
Jie Zheng ◽  
Yajing Xu ◽  
Jian Gao ◽  
Lingling Fan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Inflammatory Cells ◽  
Interleukin 10 ◽  
Chinese Han ◽  
Pcr Rflp ◽  
Different Populations ◽  
The Relationship ◽  
Diabetes Patients

Abstract The levels of cytokines, inflammatory cells, and angiogenic factors increase following diabetic retinopathy (DR), and the association between interleukin-10 (IL-10) gene rs1800896 polymorphism (IL-10 -1082G/A polymorphism) and DR in different populations has been extensively studied. However, the findings are conflicting, and there is no relevant research in Chinese subjects. Therefore, this case–control study involving 327 cases (type 2 diabetes patients with proliferative DR (PDR)) and 461 controls (type 2 diabetes patients without DR) was conducted to address the relationship between IL-10 gene rs1800896 polymorphism and risk of PDR in Chinese population. Genotyping was performed using PCR-based restriction fragment length polymorphism (PCR-RFLP) assay. It was found that GG genotype or G allele of the IL-10 gene rs1800896 polymorphism was associated with decreased risk for PDR. In conclusion, IL-10 gene rs1800896 polymorphism decreases the risk of PDR.

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