Search results for " transcription"
showing 10 items of 810 documents
Injection of Donor-Derived OX62+ Splenic Dendritic Cells With Anti-CD4 Monoclonal Antibody Generates CD4+CD25+FOXP3+ Regulatory T Cells That Prolong …
2009
Abstract Objective To examine in a rat model the ability of donor dendritic cells and anti-CD4 monoclonal antibody (mAb) to generate donor-specific CD4+CD25+ regulatory T cells (Tregs) and to evaluate the capacity of these Tregs to prolong skin allograft survival and abrogate the production of donor-specific antibodies after skin grafting. Materials and Methods OX62+ (nonplasmacytoid) splenic dendritic cells were isolated from Fischer rats using magnetic beads and injected (2 × 10 6 ) into Lewis rat recipients with or without treatment with a nondepleting anti-CD4 (W3/25) mAb. After 4 weeks, splenic CD4+CD25+FOXP3+ T cells were harvested using magnetic beads from conditioned animals and inj…
Expression of Wild-Type and Variant Estrogen Receptor Alpha in Liver Carcinogenesis and Tumor Progression.
2011
Although estrogen receptors (ERs) are expressed in human hepatocellular carcinoma (HCC), several clinical trials have failed to demonstrate the efficacy of antiestrogen treatment in HCC patients. Recently, the identification of several ER splicing variants has enlightened the complex nature of estrogen signaling in peripheral tissues; this may help understanding estrogen role in either nontumoral or malignant nonclassical target organs, including liver. In this work we have investigated mRNA expression of wild-type and splice variants of ERα in nontumoral, cirrhotic, and malignant human liver, as well as in HCC cell lines, using an exon-specific reverse transcription polymerase chain reacti…
Distinct subsets of regulatory T cells during pregnancy: is the imbalance of these subsets involved in the pathogenesis of preeclampsia?
2008
Abstract Regulatory T cells (CD4 + CD25 + FoxP3 + -Treg cells) are important regulators of tolerance induction during pregnancy. We now found that the number of CD4 + CD25 + FoxP3 + -Treg cells decreases during normal course of pregnancy and even more so in women affected by preeclampsia. The functional activity of these CD4 + CD25 + -Treg cells was significantly reduced in comparison to those of healthy pregnants. Further analysis revealed two Treg subsets that differed with regard to the FoxP3 and CD25 expression. The percentage of both, CD4 + CD25 + FoxP3 high+ -Treg and CD4 + CD25 high+ FoxP3 + , was maximal in the first and second trimenon, but declined severely in the third trimenon. …
Small for gestational age (SGA) neonates show reduced suppressive activity of their regulatory T cells
2009
Little information exists concerning the role of fetal regulatory T cells (Tregs) during intrauterine development. We examined whether complications such as reduced birth weight or the occurrence of preterm labor were associated with deficiencies in the number or in the immunosuppressive activity of Tregs in the fetal circulation. Their total number did not change during normal or complicated pregnancy. In contrast, their level of FoxP3 expression decreased continuously with gestational age and was significantly reduced in the presence of spontaneous term, but not preterm labor. In small for gestational age (SGA) neonates, FoxP3 expression was constantly decreased when compared to age match…
Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus
2013
The author manuscript of this article is open access and is freely available online at PubMed Central
Tetralogy of Fallot as a Model to Study Cardiac Progenitor Cell Migration and Differentiation During Heart Development
2009
Tetralogy of Fallot (ToF) has long been considered a congenital disorder that occurs due to environmental alterations during gestation. Recently, several mutated genes have been discovered that are thought to be responsible for the malformations observed in ToF. These genetic mutations, which are microdeletions, are sporadic and are frequently also present in trisomy 21 patients. The ToF malformations can be lethal, but for the last 50 years, surgical repairs that place an artificial patch to repair the four features of ToF have improved the survival of patients with ToF. However, 0.5% to 6% of patients who survive after surgical repair of ToF die of sudden cardiac death caused by ventricul…
Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells
2011
Abstract The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP repression, however,…
Retarded thymic involution and massive germinal center formation in NF-ATp-deficient mice.
1998
NF-ATp and NF-ATc are the most prominent nuclear NF-AT transcription factors in peripheral T lymphocytes. After T cell activation both factors bind to and control the promoters and enhancers of numerous lymphokine and receptor ligand genes. In order to define a specific role for NF-ATp in vivo we have inactivated the NF-ATp gene by gene targeting in mice. We show that NF-ATp deficiency leads to the accumulation of peripheral T cells with a “preactivated” phenotype, enhanced immune responses of T cells after secondary stimulation in vitro and severe defects in the proper termination of antigen responses, as shown by a reduced deletion of superantigen-reactive CD4+ T cells. These alterations …
Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner – A quantitative in vitro gene expression analy…
2010
Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ). There are two groups of bisphosphonates: the nitrogen-containing bisphosphonates, e.g. zoledronate and ibandronate, and the non-nitrogen-containing bisphosphonates, e.g. clodronate. Their impact on bone metabolism seems to differ. The objective of this study was to compare the osteogenic differentiation potency of these two pharmacologic groups. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5×10(-5) M, 5×10(-6) M and 5×10(-7) M over the experimental …
Sox17 regulates liver lipid metabolism and adaptation to fasting.
2014
Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is …