Search results for "Regulatory"
showing 10 items of 740 documents
TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic …
2009
TLRs represent the first line of defense against invading pathogens in the innate immune system. Certain cytokines are important mediators and essentially necessary to assure an appropriately regulated immune response. Recent data gave initial evidence that IL-1beta is one of the most relevant members of these regulating cytokines. We investigated the induction of IL-1beta production in monocytes and pDCs stimulated with ligands for TLR7 and TLR8 and with antiphospholipid antibodies (aPL). Using human monocytes and pDCs for stimulation with specific TLR7 and TLR8 ligands such as resiquimod (R848) and single stranded RNA (RNA42) as well as with a human monoclonal aPL HL5B resulted in a speci…
Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease
2015
Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (↑LDLR, ↓MYLIP), synthesis (↑SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (↓A…
Evaluation of the therapeutic potential of PPARalpha agonists for X-linked adrenoleukodystrophy.
2003
Adrenoleukodystrophy protein (ABCD1), a peroxisomal membrane protein, is mutated in patients affected by X-linked adrenoleukodystrophy (X-ALD). Adrenoleukodystrophy-related protein (ABCD2) is the closest relative of ABCD1. Pharmacological induction of ABCD2 gene expression has been proposed as a novel therapy strategy for X-ALD. Fibrates induce peroxisome proliferation and Abcd2 expression in rodent liver. Here we evaluate the possibility of using peroxisome proliferator-activated receptor alpha (PPARalpha) agonists for pharmacological induction of ABCD2 expression. In the liver of PPARalpha-deficient mice, both the constitutive and the fenofibrate-inducible Abcd2 gene expression was found …
Paracrine Activation of Hepatic CB1 Receptors by Stellate Cell-Derived Endocannabinoids Mediates Alcoholic Fatty Liver
2008
SummaryAlcohol-induced fatty liver, a major cause of morbidity, has been attributed to enhanced hepatic lipogenesis and decreased fat clearance of unknown mechanism. Here we report that the steatosis induced in mice by a low-fat, liquid ethanol diet is attenuated by concurrent blockade of cannabinoid CB1 receptors. Global or hepatocyte-specific CB1 knockout mice are resistant to ethanol-induced steatosis and increases in lipogenic gene expression and have increased carnitine palmitoyltransferase 1 activity, which, unlike in controls, is not reduced by ethanol treatment. Ethanol feeding increases the hepatic expression of CB1 receptors and upregulates the endocannabinoid 2-arachidonoylglycer…
A non-redundant role for OX40 in the competitive fitness of Treg in response to IL-2.
2010
OX40 stimulation is known to enhance activation of effector T cells and to inhibit induction and suppressive function of Treg. Here we uncovered a novel role of OX40 in sustaining Treg competitive fitness in vivo, during repopulation of lymphopenic hosts and reconstitution of BM chimeras. Defective expansion of OX40-null Treg diminished their ability to suppress inflammation in a model of lymphopenia-driven colitis. OX40-mediated promotion of Treg fitness spanned beyond lymphopenic environments, as endogenous Treg in OX40-null mice showed decreased accumulation during thymic development, enhanced susceptibility to antibody-mediated depletion and defective turnover following thymectomy. In v…
Does enterprise social media use promote employee creativity and well-being?
2021
Abstract Despite the increased use of Enterprise Social Media (ESM) worldwide, its adverse impact on firms’ employees, such as exhaustion, has not been researched sufficiently. This is a critical gap in the literature since employees’ well-being is crucial to maintaining their productivity. The current study addresses this gap by examining whether interruption overload and psychological transition affect the relationship of employees’ socio-instrumental use of ESM with ESM-related exhaustion and employee creativity, respectively. We utilized the Conservation of Resources (COR) theory to conceptualize the mediation effect of interruption overload and psychological transition on the hypothesi…
mBISON: Finding miRNA target over-representation in gene lists from ChIP-sequencing data
2015
Background Over-representation of predicted miRNA targets in sets of genes regulated by a given transcription factor (e.g. as defined by ChIP-sequencing experiments) helps to identify biologically relevant miRNA targets and is useful to get insight into post-transcriptional regulation. Findings To facilitate the application of this approach we have created the mBISON web-application. mBISON calculates the significance of over-representation of miRNA targets in a given non-ranked gene set. The gene set can be specified either by a list of genes or by one or more ChIP-seq datasets followed by a user-defined peak-gene association procedure. mBISON is based on predictions from TargetScan and us…
Increased innate and adaptive immune responses in induced sputum of young smokers
2015
Background and objectives: It is known that chronic obstructive pulmonary disease (COPD) development process is imperceptible and can be asymptomatic for 20 or more years. It is of great importance to diagnose early inflammatory changes that can lead to COPD in young asymptomatic cigarette smokers. The aim of our study was to analyze the cell spectrum of induced sputum (IS) of young cigarette smokers, with emphasis on T-regulatory cells. Materials and methods: A total of 20 healthy nonallergic smokers, 20 nonsmokers and 20 COPD patients were enrolled in the study. After lung function measurements were taken, we performed sputum induction and analyzed sputum cells. We evaluated the cell coun…
Class IIa HDACs repressive activities on MEF2-depedent transcription are associated with poor prognosis of ER⁺ breast tumors.
2013
MEF2s transcription factors and class IIa HDACs compose a fundamental axis for several differentiation pathways. Functional relationships between this axis and cancer are largely unexplored. We have found that class IIa HDACs are heterogeneously expressed and display redundant activities in breast cancer cells. Applying gene set enrichment analysis to compare the expression profile of a list of putative MEF2 target genes, we have discovered a correlation between the down-regulation of the MEF2 signature and the aggressiveness of ER(+) breast tumors. Kaplan-Meier analysis in ER(+) breast tumors evidenced an association between increased class IIa HDACs expression and reduced survival. The im…
Combined Stress Conditions in Melon Induce Non-additive Effects in the Core miRNA Regulatory Network
2021
Climate change has been associated with a higher incidence of combined adverse environmental conditions that can promote a significant decrease in crop productivity. However, knowledge on how a combination of stresses might affect plant development is still scarce. MicroRNAs (miRNAs) have been proposed as potential targets for improving crop productivity. Here, we have combined deep-sequencing, computational characterization of responsive miRNAs and validation of their regulatory role in a comprehensive analysis of response of melon to several combinations of four stresses (cold, salinity, short day, and infection with a fungus). Twenty-two miRNA families responding to double and/or triple …