Equine herpesvirus 1 (EHV-1) is the causative agent of a number of equine pathological states, including severe disease of the central nervous system, respiratory infections, and abortion storms. Our results showed that intranasal immunization with CpG-B oligodeoxynucleotides (ODN) protects CBA mice from lethal EHV-1 challenge. IFN-γ and seven interferon-stimulated genes (ISGs) were upregulated 39.4- to 260.3-fold at 8 h postchallenge in the lungs of RacL11-challenged mice that had been immunized with CpG-B ODN. Treatment with 20 ng/ml of IFN-γ reduced EHV-1 yield by 100-fold in MH-S at 4 days post-VZV infection compared to that of untreated cells. However, IFN-γ reduced virus yield by only 2-fold in and mouse fibroblast L-M cells. To identify IFN-γ-stimulated genes that inhibit EHV-1 replication, Affymetrix microarray analyses were performed with IFN-γ-treated MH-S and L-M cells. In MH-S cells, IFN-γ upregulated 551 genes and down-regulated 136 genes as compared to those of untreated cells. In L-M cells, IFN-γ upregulated 225 genes and downregulated 2 genes. Nine genes associated with innate immune response were significantly upregulated only in MH-S cells. Five antiviral ISGs MX1, SAMHD1, NAMPT, TREX1, and DDX60 were upregulated 3.2- to 18.1-fold only in MH-S cells. These results suggest that CpG-B ODN may be used as a prophylactic agent in horses.
Interferon Gamma Inhibits Equine Herpesvirus 1 Replication in a Cell Line-Dependent Manner.
Specimen part, Cell line, Treatment
View SamplesMicroRNA regulates protein expression of cells by repressing translation of specific target messenger transcripts. Loss of the neuron specific microRNA miR-128 in Dopamine D1-receptor expressing neurons in the murine striatum (D1-MSNs) lead to increased neuronal excitability, locomotor hyperactivity and fatal epilepsy.
MicroRNA-128 governs neuronal excitability and motor behavior in mice.
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View SamplesMammalian microRNAs (miRNAs) are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the mir-155-induced GM populations displayed pathological features characteristic of myeloid neoplasia. Extending possible relevance to human disease, miR-155 was overexpressed in the bone marrow of patients with acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress.
Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder.
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View SamplesWe used microarrays to look at overall gene expression differences between miR-155-/- and WT dendritic cells under inflammatory conditions.
MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development.
Specimen part
View SamplesPolymorphisms in the interleukin-4 receptor chain (IL-4R) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4R has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target and tissue-specific manner to mediate heightened expression of a subset of IL-4 and IL-13responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4Rdependent signaling.
Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma.
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