Gene expression profile of IFNα transgenic mice
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ABSTRACT:
PROVIDER: PRJNA509227 | ENA |
REPOSITORIES: ENA
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Project description:The cause of systemic lupus erythematosus (SLE) is unknown. Interferonα (IFNα) has been suggested as a causative agent of SLE, however, it is not proven, and to what extent and how IFNα contributes to the disease is unknown. We here directly studied the contribution of IFNα to SLE by generating inducible IFNα transgenic mice which showed that conditional up-regulation of IFNα induced a typical manifestation of SLE including serum immune complex (IC), autoantibody against double stranded DNA (anti-dsDNA Ab) and the organ manifestations classical to SLE such as IC-deposited glomerulonephritis, classical splenic onion-skin lesion, and alopecia, epidermal liquefaction, positive lupus-band test of the skin. In the spleen of mice, activated effector CD4 T cells, interferonγ-producing CD8 T cells, B220+CD86+ cells and CD11c+CD86+ cells were increased, and the T cells produced increased amounts of IL-4, IL-6, IL-17 and IFNγ and decreased IL-2. In particular, activated CD3+CD4-CD8- double-negative T (DNT) cells positive for TCRαβ, B220, CD1d-teteramer, PD-1 and Helios, which produced increased amounts of IFNγ, IL-4, IL-17 and TNFα, were significantly expanded. They infiltrated into kidney and induced de novo glomerulonephritis and alopecia when transferred into naïve recipients. Thus, conditional up-regulation of IFNα is sufficient to induce SLE, and the DNT cells as expanded by IFNα are directly responsible for the organ manifestations such as lupus skin disease or nephritis.
2018-12-10 | GSE123549 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE17299: Direct effects of IFNα on human CD8 T cells_without any other concomitant signals GSE17301: The effect of IFNα on human CD8 T cells_with other concomitant signals Refer to individual Series
2010-07-23 | E-GEOD-17302 | biostudies-arrayexpress
Project description:Type I interferon is naturally produced in response to pathogens to generate an anti-viral state within the cell. There are 13 naturally occurring genetic isoforms of IFN alpha (IFNα) in humans that result in 12 IFNα subtypes (IFNα1 and α13 are identical but are coded by different genes). They all bind the same ubiquitously expressed receptor, interferon alpha receptor (IFNAR), but have been shown to differ in their biological and anti-viral activities (reviewed in Gibbert et al, Br J Pharmacol 2013). We investigated the ability of natural and recombinant IFNα to regulate mRNA expression. Here we present a dataset comprising whole genome microarray data from primary human monocyte-derived macrophages following treatment with different preparations of IFNα. These data are suitable for determination of IFN-stimulated genes, and additionally allow differential analysis of gene induction in response to natural versus recombinant IFNα. For example, this comparison may be useful in identifying cellular anti-viral effector proteins involved in viral restriction, thus potentially providing novel therapeutic approaches without the historical negative outcomes of IFNα therapy.
2019-10-31 | GSE54455 | GEO
Project description:Apolipoprotein A-I mimetic peptides are amphipathic alpha-helix peptides that display similar functions to apolipoprotein A-I. Preclinical and clinical studies have demonstrated the safety and efficacy of apolipoprotein A-I mimetic peptides in multiple indications associated with inflammatory processes. In this study, we evaluated the effect of the long-term expression of L37pA in the liver by an adeno-associated virus (AAV-L37pA) on the expression of an adeno-associated virus encoding interferon-alpha (AAV-IFNα). Long-term IFNα expression in the liver leads to lethal hematological toxicity one month after AAV administration. Concomitant administration of AAV-L37pA prevented the lethal toxicity since the IFNα expression was reduced one month after AAV administration by decreasing the expression of IFNα. To identify the mechanism of action of L37pA, a genomic and proteomic analysis was performed fifteen days after AAV administration when a similar level of IFNα and interferon-stimulated genes were observed in mice treated with AAV-IFNα alone and in mice treated with AAV-IFNα and AAV-L37pA. The coexpression of the apolipoprotein A-I mimetic peptide L37pA with IFNα modulated the gene expression program of IFNα, inducing a significant reduction in inflammatory pathways affecting pathogen-associated molecular patterns receptor, dendritic cells, NK cells and Th1 immune response. The proteomic analysis confirmed the impact of the L37pA activity on several inflammatory pathways and indicated an activation of LXR/RXR and PPPARα/γ nuclear receptors. Thus, long-term expression of L37pA induces an anti-inflammatory effect in the liver that allows silencing of IFNα expression mediated by an adeno-associated virus.
2021-09-09 | PXD023281 | Pride
Project description:Expression of PS19 Tau Transgenic mice from hippocampus at different ages 3, 6, 9, and 12 months We used Affy arrays to understand the global expression profile of PS19 Tau transgenic mice
2018-08-28 | GSE89979 | GEO
Project description:Gene expression in fra-2 transgenic mice
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Project description:Background The in vivo properties of HR-HPV E6 and E7 oncoproteins have been previously evaluated through the generation and characterization of HPV transgenic mouse strains. Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. Taken together, these findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues. We evaluated the different expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with corresponding tissues from non-transgenic (FVB) mice. Result Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation in pro-apoptotic genes expression, particularly in those related to the extrinsic apoptotic pathway. In contrast, we observed up-regulation of anti-apoptotic genes. Another pathway that was severely affected in skin was the immune response. In cervix from transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways. Interestingly, we observed alterations in the expression of immune response genes in cervix from K14E6 transgenic mice. Pathways such as angiogenesis, cell junction, cytoskeleton, keratinocyte differentiation and epidermis development, showed different gene expression in skin or cervix from K14E6 transgenic mice. Conclusion Alterations in gene expression identified in the current study might partially explain why our K14E6 transgenic mice present a more aggressive phenotype in the skin than in the cervix. Expression of the HPV16 E6 oncoprotein alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis and the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets. Keywords: Human_papillomavirus, transgenic mice, expression profile
2008-09-01 | GSE10702 | GEO
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Project description:In order to identify IFNα-induced host factor(s) that might inhibit replication of unadapted chimeric SIV/HIV-1 viruses (SHIVs), we measured IFNα-induced gene expression in immortalized pig-tailed macaque (Ptm) CD4+ lymphocytes. Triplicate cultures of Ptm lymphocytes were left untreated or treated with 1000 U/ml of IFNα. Twenty-four hours later, RNA was isolated, and RNA-seq libraries were prepared for sequencing. A total of 198 genes were found to be significantly differentially expressed (|logFC| ≥ 0.585 & FDR 5%) upon IFNα treatment. 147/198 genes were found to be significantly upregulated and 51/198 genes were found to be significantly downregulated regulated upon IFNα treatment.
2019-06-24 | GSE126594 | GEO
Project description:Bile acids are not only physiological detergents facilitating nutrient absorption, but also signaling molecules regulating metabolic homeostasis. We reported recently that transgenic expression of CYP7A1 in mice stimulated bile acid synthesis and prevented Western diet-induced obesity, insulin resistance and hepatic steatosis. The aim of this experiment is to determine the impact of induction of hepatic bile acid synthesis on liver metabolism by determining hepatic gene expression profile in CYP7A1 transgenic mice. CYP7A1 transgenic mice and wild type control mice were fed either standard chow diet or high fat high cholesterol Western diet for 4 month. Hepatic gene expressions were measured by microarray analysis. Our results indicate that hepatic bile acid synthesis is closely linked to cholesterogenesis and lipogenesis, and maintaining bile acid homeostasis is improtant in hepatic metabolic homeostasis.
2013-08-15 | GSE38872 | GEO