Niveles plasmáticos de citoquinas IL-1ß, IL2 e IL-4 en niños diabéticos tipo 1 de diagnóstico reciente y su asociación con anticuerpos ß pancreáticos

B, Francisco Pérez; A, Amaya Oyarzún; P, Elena Carrasco; Burwinkel, Barbara; B, Cecilia Albala

doi:10.4067/s0034-98872004000400002

Cited by 12 publications

(9 citation statements)

References 39 publications

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“…The intermediary steps from hyperglycemia to TLR2 and NLRP3 activation may involve the release of endogenous TLR2 ligands43 and the generation of oxidative stress44. The increase in both TLR2 and IL-1β expression in diabetic patients454647 suggests that this mechanism of sterile inflammation is active in the natural course of disease.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

et al. 2016

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Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity. IL-1β-induced spontaneous contractile events are associated with CaMKII oxidation and phosphorylation. We further show that DM-induced arrhythmias can be successfully treated by inhibiting the IL-1β axis with either IL-1 receptor antagonist or by inhibiting the NLRP3 inflammasome. Our results establish IL-1β as an inflammatory connection between metabolic dysfunction and arrhythmias in DM.

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Section: Discussionmentioning

confidence: 99%

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

et al. 2016

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“…The IL-1 pathway has previously been implicated in humans with T1D (16–19) as well as in animal models of the disease (20). We recently reported that monocytes and mDCs from newly diagnosed patients with T1D have an altered TLR-induced IL-1 pathway (11).…”

Section: Resultsmentioning

confidence: 99%

Dysregulated Toll-Like Receptor–Induced Interleukin-1β and Interleukin-6 Responses in Subjects at Risk for the Development of Type 1 Diabetes

et al. 2012

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We tested the hypothesis that altered Toll-like receptor (TLR) signaling may be involved in early stages of type 1 diabetes (T1D). To do so, we analyzed TLR-induced interleukin (IL)-1β and IL-6 responses in freshly isolated peripheral blood mononuclear cells (PBMNCs) from seropositive compared with seronegative subjects. Similar frequencies of myeloid dendritic cells (mDCs), plasmacytoid DCs (pDCs), and monocytes were observed in seropositive and seronegative subjects. Subjects with autoantibodies had increased proportions of monocytes expressing IL-1β ex vivo. Activating PBMNCs with TLR3, TLR4, or TLR7/8 agonists in vitro led to increased percentages of IL-1β–expressing monocytes and mDCs from seropositive versus seronegative subjects. TLR ligation also resulted in a diminished IL-6 response in seropositive individuals as lower frequencies of IL-6–expressing monocytes and mDCs were induced. The dysregulated TLR-induced IL-1β and IL-6 pathways were more readily detectable in children aged <11 years and from 11 to <21 years, respectively, and did not involve altered HbA1c or the presence of one or more autoantibodies. Finally, subjects with autoantibodies had lower amounts of serum chemokine (C-X-C motif) ligand 10 compared with autoantibody-negative subjects. Our data may imply that alterations in innate immune pathways are detectable in genetically susceptible individuals and could be linked with the early course of T1D.

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“…Children positive for islet autoantibodies, indicating a genetic predisposition to diabetes, display elevated circulating IL-1β [72]. In addition, IL-1β is also increased in children recently diagnosed with T1DM [73]. …”

Section: 1 Discussionmentioning

confidence: 99%

CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic β-cells

Burke

Karlstad

Regal

et al. 2015

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Enhanced leukocytic infiltration into pancreatic islets contributes to inflammation-based diminutions in functional β-cell mass. Insulitis (aka islet inflammation), which can be present in both T1DM and T2DM, is one factor influencing pancreatic β-cell death and dysfunction. IL-1β, an inflammatory mediator in both T1DM and T2DM, acutely (within 1h) induced expression of the CCL20 gene in rat and human islets and clonal β-cell lines. Transcriptional induction of CCL20 required the p65 subunit of NF-κB to replace the p50 subunit at two functional κB sites within the CCL20 proximal gene promoter. The NF-κB p50 subunit prevents CCL20 gene expression during unstimulated conditions and overexpression of p50 reduces CCL20, but enhances cyclooxygenase-2 (COX-2), transcript accumulation after exposure to IL-1β. We also identified differential recruitment of specific co-activator molecules to the CCL20 gene promoter, when compared with the CCL2 and COX2 genes, revealing distinct transcriptional requirements for individual NF-κB responsive genes. Moreover, IL-1β, TNF-α and IFN-γ individually increased the expression of CCR6, the receptor for CCL20, on the surface of human neutrophils. We further found that the chemokine CCL20 is elevated in serum from both genetically obese db/db mice and in C57BL6/J mice fed a high-fat diet. Taken together, these results are consistent with a possible activation of the CCL20-CCR6 axis in diseases with inflammatory components. Thus, interfering with this signaling pathway, either at the level of NF-κB-mediated chemokine production, or downstream receptor activation, could be a potential therapeutic target to offset inflammation-associated tissue dysfunction in obesity and diabetes.

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Niveles plasmáticos de citoquinas IL-1ß, IL2 e IL-4 en niños diabéticos tipo 1 de diagnóstico reciente y su asociación con anticuerpos ß pancreáticos

Abstract: Background: Type 1 diabetes is an organ specifc autoimmune disease whose incidence is increasing worldwide. A functional imbalance in cytokine production resulting in dominance of (Rev Méd Chile 2004; 132: 413-20).

Cited by 12 publications

References 39 publications

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

Macrophage-dependent IL-1β production induces cardiac arrhythmias in diabetic mice

Dysregulated Toll-Like Receptor–Induced Interleukin-1β and Interleukin-6 Responses in Subjects at Risk for the Development of Type 1 Diabetes

CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic β-cells

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