Differential regulation of pro-inflammatory cytokine signalling by protein tyrosine phosphatases in pancreatic β-cells

Stanley, William J; Trivedi, Prerak; Sutherland, Andrew P. R.; Thomas, Helen; Gurzov, Esteban Nicolas

doi:10.1530/jme-17-0089

Cited by 9 publications

(8 citation statements)

References 61 publications

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“…Importantly, PTPN1 inactivation by pharmacological modulation protects β-cells and primary mouse islets from cytokine-mediated cell death. These data point to a non-redundant effect of PTP regulation of cytokine signalling in β-cells in autoimmune diabetes [55].…”

Section: Applicationmentioning

confidence: 69%

CRISPR/Cas9 system - a revolution in gene editing

Adamov¹,

Georgiev²,

Daneva³

2018

Med Case Rep Rev

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CRISPR/Cas9 technology, is a fundamental and very important discovery for modern biology which we consider simply as a way of editing the genome. It lies in the fact that a huge number of bacteria carry in their genome an effective system of adaptive immunity against potential viral invasion. The basis of this system is special genome regions -short palindromic cluster repeats or CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats).Ultimately, CRISPR/Cas9 technology can change the standpoint of humanity to many different hereditary diseases. If earlier they were either completely incurable, or they allowed palliative, symptomatic treatment, now it is possible to treat them by manipulating individual genes, that is, to eliminate the very cause of the respective disease. Simultaneously with the advent of genome editing technology, the possibility of its "improvement" appears, in a variety of ways. So far fairly simple (from the point of view of the inheritance mechanism) diseases, and not only mutated genes can be potentially targets for editing, as well as numerous genes associated with an increased risk to human health. Much additional work remains to be done in the areas nucleotide manipulation and replacement before the full therapeutic potential of these approaches can be realized. Of equal importance, all moral and ethical issues related to gene editing therapies must be taken in account before any practical approach is applied.

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Section: Applicationmentioning

confidence: 69%

CRISPR/Cas9 system - a revolution in gene editing

Adamov¹,

Georgiev²,

Daneva³

2018

Med Case Rep Rev

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show abstract

Section: Applicationmentioning

confidence: 70%

Crispr/Cas9 System - A Revolution in Gene Editing

Adamov

Georgiev

Daneva

et al. 2018

BJSTR

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“…Some studies reported that ablation or blockage of IFN-γ causes delayed or decreased incidence of T1D (14). IFN-γ has been found to increase the toxic effects of macrophages and T lymphocytes on β cell function (15)(16)(17). Improvement in β cell function in T1D is considered to be a result of insulin sensitivity and reduced inflammatory/autoimmune process in islets (18).…”

Section: Discussionmentioning

confidence: 99%

T Helper 1 Cytokines and Their Relationship with Beta Cell Function in Type 1 Diabetes

Tamer¹,

Başok²,

Doğan³

et al. 2020

Turk J Endocrinol Metab

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Objective: In type 1 diabetes (T1D), T helper (Th) 1 cells affect β cell functions significantly. This study aims to explore the association between serum levels of Th1 cytokines [interferon-gamma (IFN-γ), interleukin (IL)-2 and tumor necrosis factor-alpha (TNF-α)] and β cell function in T1D. Material and Methods: The study included 110 patients with T1D (TIDPs) and 31 healthy controls. The β cell functions in T1DPS were assessed by calculating mixed-meal stimulated C-peptide levels. T1DPs were categorized into three groups depending on results of this test (1a-lowest, 1b, 1chighest). Cytokine levels, IFN-γ/IL-2, and TNF-α/IL-2 ratios in T1DPs were compared with that in controls. Correlation analysis between cytokine levels and diabetes-related parameters was then carried out. Results: IFN-γ, TNF-α, IL-2 levels, and TNF-α/IL-2 of T1DPs were higher (p=0.02, p=0.01, p=0.008, and p=0.01, respectively) than that of controls. The highest IFN-γ/IL-2 and TNF-α/IL-2 ratios were observed in group 1b (p=0.03 and p=0.04, respectively) while the lowest IFN-γ/IL-2 and TNF-α/IL-2 ratios were observed in group 1a (p=0.03 and p=0.04, respectively). The TNF-α levels were found to be negatively correlated with fasting glucose levels (r 2 =-0.003, p=0.031). However, after adjustment for age and gender, this correlation diminished (r 2 =-0.028, p=0.076). Conclusion: IFN-γ, IL-2, and TNF-α may exhibit a triggering role in the pathogenesis of T1D. IFN-γ/IL-2 and TNF-α/IL-2 ratios possibly have more significant roles in the progression of β cell dysfunction than other cytokines (Clini-calTrials.gov number: NCT02389335).

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Differential regulation of pro-inflammatory cytokine signalling by protein tyrosine phosphatases in pancreatic β-cells

Cited by 9 publications

References 61 publications

CRISPR/Cas9 system - a revolution in gene editing

CRISPR/Cas9 system - a revolution in gene editing

Crispr/Cas9 System - A Revolution in Gene Editing

T Helper 1 Cytokines and Their Relationship with Beta Cell Function in Type 1 Diabetes

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