Search results for "Transduction"
showing 10 items of 2149 documents
Total synthesis and biological evaluation of the natural product (−)-cyclonerodiol, a new inhibitor of IL-4 signaling
2014
In a screening program of natural compounds from fungi, the known cyclopentanoid sesquiterpene (-)-cyclonerodiol was identified as a specific inhibitor of the IL-4 induced STAT6 signaling pathway (IC50 = 9.7 μM) which is required for the differentiation of naive CD4 T cells to T helper type 2 (Th2) lymphocytes. As many allergic conditions, including allergic asthma and atopic diseases, are driven by an excessive Th2 response, STAT6 is a promising target for the development of new therapeutics. The compound was synthesized in six steps from (-)-linalool using an epoxide radical cyclization as the key step.
Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway.
2014
Abstract Dendritic cells (DC) are one target for immune suppression by regulatory T cells (Treg), because their interaction results in reduced T cell stimulatory capacity and secretion of inhibitory cytokines in DC. We show that DC in the presence of Treg are more mobile as compared with cocultures with conventional CD4+ T cells and form DC–Treg aggregates within 2 h of culture. The migration of DC was specifically directed toward Treg, as Treg, but not CD4+ T cells, attracted DC in Boyden chambers. Treg deficient for the ectonucleotidase CD39 were unable to attract DC. Likewise, addition of antagonists for A2A adenosine receptors abolished the formation of DC–Treg clusters, indicating a ro…
Neuroimmune Activation and Myelin Changes in Adolescent Rats Exposed to High-Dose Alcohol and Associated Cognitive Dysfunction: A Review with Referen…
2014
Aims: The aim of the study was to assess whether intermittent ethanol administration to adolescent rats activates innate immune response and TLRs signalling causing myelin disruption and long-term cognitive and behavioural deficits. Methods: We used a rat model of intermittent binge-like ethanol exposure during adolescence. Results: Binge-like ethanol administration to adolescent rats increased the gene expression of TLR4 and TLR2 in the prefrontal cortex (PFC), as well as inflammatory cytokines TNF alpha and IL-1 beta. Up-regulation of TLRs and inflammatory mediators were linked with alterations in the levels of several myelin proteins in the PFC of adolescent rats. These events were assoc…
TCTN3 Mutations Cause Mohr-Majewski Syndrome
2012
Orofaciodigital syndromes (OFDSs) consist of a group of heterogeneous disorders characterized by abnormalities in the oral cavity, face, and digits and associated phenotypic abnormalities that lead to the delineation of 13 OFDS subtypes. Here, by a combined approach of homozygozity mapping and exome ciliary sequencing, we identified truncating TCTN3 mutations as the cause of an extreme form of OFD associated with bone dysplasia, tibial defect, cystic kidneys, and brain anomalies (OFD IV, Mohr-Majewski syndrome). Analysis of 184 individuals with various ciliopathies (OFD, Meckel, Joubert, and short rib polydactyly syndromes) led us to identify four additional truncating TCTN3 mutations in un…
Research in practice: Regulatory T cells - targets for therapeutic approaches?
2010
• regulatory T cells • tolerance • signal transduction • autoimmunity • allergies • cancer Summary Regulatory T cells (Tregs) are essential for induction and maintenance of immunological tolerance. They contribute to prevention of autoimmunity by control and modulation of immune responses. The prevalence of autoimmune diseases, chronic infections, cancer and allergies has markedly increased in the last decades. In additions the treatment of these disorders is often unsatisfactory so that improvements are needed. This has stimulated intensive research in the biology of Tregs. Recent studies revealed that naturally occurring CD4 + CD25 + Tregs (nTregs) and induced Tregs (iTregs) are critical …
Contribution of IL-17-producing {gamma}{delta} T cells to the efficacy of anticancer chemotherapy.
2011
IL-17 production by γδ T cells is required for tumor cell infiltration by IFN-γ–producing CD8+ T cells and inhibition of tumor growth in response to anthracyclines.
Coexpression of TGF-β1 and IL-10 Enables Regulatory T Cells to Completely Suppress Airway Hyperreactivity
2008
Abstract In allergic airway disease, Treg may play an important role in the modulation of airway hyperreactivity (AHR) and inflammation. We therefore investigated the therapeutic potential of Treg in an Ag-dependent murine asthma model. We here describe that AHR can be completely suppressed by adoptive transfer of Treg overexpressing active TGF-β1. Using mice with impaired TGF-β signaling in T cells, we could demonstrate that TGF-β signaling in recipient effector T cells or transferred Treg themselves is not required for the protective effects on AHR. However, the expression of IL-10 by Treg was found to be essential for the suppression of AHR, since Treg overexpressing active TGF-β1 but de…
Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway
2016
// Daniela Massihnia 1,* , Antonio Galvano 1,* , Daniele Fanale 1 , Alessandro Perez 1 , Marta Castiglia 1 , Lorena Incorvaia 1 , Angela Listi 1 , Sergio Rizzo 1 , Giuseppe Cicero 1 , Viviana Bazan 1 , Sergio Castorina 2,3,** and Antonio Russo 1,** 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 Fondazione Mediterranea “G.B. Morgagni”, Catania, Italy 3 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy * These authors have contributed equally to this work ** Both the authors are last name Correspondence to: Antonio Russo, email: // Keywords : ER, HER2, PI3K/AKT/mTOR inhib…
Association of Klotho Polymorphisms with Healthy Aging: A Systematic Review and Meta-Analysis
2013
Today it is clearly evident that genetic background constitutes an integral part of aging and longevity. Many studies on long-lived people have been conducted emphasizing the role of certain genes in long life. Classic case-control studies, genome-wide association studies, and high-throughput sequencing have permitted identification of a variety of genetic variants seemingly associated with longevity. Over the years, aging research has focused on the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway because of its evolutionarily conserved correlation with life-span extension in model animals. Indeed, many single-nucleotide polymorphisms (SNPs) associated with longevity were ide…
SHIP2: A “NEW” Insulin Pathway Target for Aging Research
2014
Strong evidence suggests that systemic inflammation and central adiposity contribute to and perpetuate metabolic syndrome. All of these alterations predispose individuals to type 2 diabetes mellitus (T2DM), cardiovascular disease, as well as Alzheimer's disease (AD), all characterized by chronic inflammatory status. On the other hand, extensive abnormalities in insulin and insulin-like growth factor I (IGF-I) and IGF-II signaling mechanisms in brains with AD have been demonstrated, suggesting that AD could be a third form of diabetes. The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has an important role in the insulin pathway because its over-expression causes impairment…