Search results for "Transgenic"
showing 10 items of 552 documents
IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1
2007
IL-27 is an IL-12-related cytokine frequently present at sites of inflammation that can promote both anti- and pro-inflammatory immune responses. Here, we have analyzed the mechanisms how IL-27 may drive such divergent immune responses. While IL-27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti-inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL-27 suppressed the development of adaptive, TGF-beta-induced Forkhead box transcription factor p3-positive (Foxp3(+)) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg develo…
Production of functional IL-18 by different subtypes of murine and human dendritic cells (DC): DC-derived IL-18 enhances IL-12-dependent Th1 developm…
1998
IL-18 is a recently described cytokine that shares biological activities with IL-12 in driving the development of Th1-type T cells. As dendritic cells (DC) are very potent inducers of T cell proliferation and differentiation we wondered whether they utilize IL-18 as a factor driving Th1 development. We demonstrate by Northern blot and reverse transcription-PCR that various subtypes of human and murine DC as well as the DC-line XS contain IL-18 mRNA. When supernatants of either enriched Langerhans cells (LC) or bone marrow-derived DC were analyzed for production of IL-18 protein, IL-18 production was detected in an IL-18-specific ELISA. To assess whether the IL-18 protein released by DC is f…
Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development.
2015
International audience; Myotonic dystrophy type 1 (DM1) is caused by an unstable expanded CTG repeat located within the DMPK gene 3'UTR. The nature, severity and age at onset of DM1 symptoms are very variable in patients. Different forms of the disease are described, among which the congenital form (CDM) is the most severe. Molecular mechanisms of DM1 are well characterized for the adult form and involve accumulation of mutant DMPK RNA forming foci in the nucleus. These RNA foci sequester proteins from the MBNL family and deregulate CELF proteins. These proteins are involved in many cellular mechanisms such as alternative splicing, transcriptional, translational and post-translational regul…
Deficiency of Nrf2 accelerates the effector phase of arthritis and aggravates joint disease
2011
14 páginas, 8 figuras, 1 tabla.-- et al.
Non-conventional forms of HLA-B27 are expressed in spondyloarthritis joints and gut tissue
2016
Objectives Human leukocyte antigen (HLA)-B27 (B27) is the strongest genetic factor associated with development of Ankylosing Spondylitis and other spondyloarthropathies (SpA), yet the role it plays in disease pathogenesis remains unclear. We investigated the expression of potentially pathogenic non-conventional heavy chain forms (NC) of B27 in synovial and intestinal tissues obtained from SpA patients. We also determined the presence of NC-B27 in joints, lymphoid and gastrointestinal tissue from B27 transgenic (TG1) rats with M.tuberculosis-induced SpA. Methods Expression of NC-B27 in human SpA joints and gut and in (21-3 × 283-2)F1 HLA-B27/Huβ2m rat tissue was determined by immunohistochem…
Non-target and biological diversity risk assessment
2008
This chapter discusses the following procedures for risk assessment in Bt cotton using the non-target risk assessment model developed by scientists of the GMO ERA Project ("International Project on GMO Environmental Risk Assessment Methodologies", which is a continuation of the GMO Guidelines Project, which was launched by scientists of the International Organization for Biological Control Global Working Group on "Transgenic Organisms in Integrated Pest Management and Biological Control"): (1) identify relevant functional groups of biological diversity associated with adverse effects, (2) list and prioritize species or ecological processes, (3) identify potential exposure pathways and adver…
Functional analysis of broadly tuned odorant receptors expressed in the mouse septal organ through patch-clamp recordings in an intact preparation an…
2010
The septal organ (SO) is a small island of olfactory epithelium located at the ventral base of the nasal septum. SO neurons express identified odorant receptors, but its function remains unknown. Using perforated patch clamp recordings, we investigated the response properties of SO neurons in the intact epithelium of mice to a panel of 45 odorants or mixtures. Out of 328 neurons tested, approximately 70% responded to odor stimulation. Among the responsive neurons, 72.5 % responded to multiple odorants. Responding neurons were tested with increasing concentrations of 3 odorants (octanoic acid, (+) camphor, amylacetate) and a mixture (fox urine). Dose-response curves show nanomolar threshold …
Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
2013
Recent genome-wide association studies have linked type-2 diabetes mellitus to a genomic region in chromosome 9p21 near the Ink4/Arf locus, which encodes tumor suppressors that are up-regulated in a variety of mammalian organs during aging. However, it is unclear whether the susceptibility to type-2 diabetes is associated with altered expression of the Ink4/Arf locus. In the present study, we investigated the role of Ink4/Arf in age-dependent alterations of insulin and glucose homeostasis using Super-Ink4/Arf mice which bear an extra copy of the entire Ink4/Arf locus. We find that, in contrast to age-matched wild-type controls, Super-Ink4/Arf mice do not develop glucose intolerance with agi…
Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.
2005
Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both …
Induction of body weight loss through RNAi-knockdown of APOBEC1 gene expression in transgenic rabbits
2014
In the search of new strategies to fight against obesity, we targeted a gene pathway involved in energy uptake. We have thus investigated the APOB mRNA editing protein (APOBEC1) gene pathway that is involved in fat absorption in the intestine. The APOB gene encodes two proteins, APOB100 and APOB48, via the editing of a single nucleotide in the APOB mRNA by the APOBEC1 enzyme. The APOB48 protein is mandatory for the synthesis of chylomicrons by intestinal cells to transport dietary lipids and cholesterol. We produced transgenic rabbits expressing permanently and ubiquitously a small hairpin RNA targeting the rabbit APOBEC1 mRNA. These rabbits exhibited a moderately but significantly reduced …