Disease relevance of Ifna1

• Structure and expression in Escherichia coli of a cloned rat interferon-alpha gene [1].
• Infection of astrocytes with Newcastle disease virus stimulated the production of 1,2-diacylglycerol, and resulted in the kinase-dependent expression of mRNAs encoding tumor necrosis factor (TNF), interferon alpha and beta, and interleukin 6 [2].
• In rat cells, for instance, rat interferon alpha/beta induces three Mx proteins which all cross-react with antibody 2C12 but differ in mol. wt and intracellular location, and it protects these cells well against influenza viruses [3].
• However, when rat cells are microinjected with antibody 2C12, interferon alpha/beta cannot induce an efficient antiviral state against influenza virus infection, whereas protection against vesicular stomatitis virus is not altered [3].
• Rat interferon-alpha also reduced the growth rate of Rous sarcoma virus-transformed rat cells in a dose-dependent manner over a 72-h period [4].

Psychiatry related information on Ifna1

• Using the tail-flick induced by electro-stimulation as a pain marker, it was found that pain threshold (PT) was significantly increased after injecting interferon-alpha (IFN alpha) into the lateral ventricle of rats [5].
• The serious and characteristic side effects of interferon-alpha (IFN-alpha) therapy on the central nervous system, resulting in such problems as affective disorders or parkinsonism, have led us to investigate the biochemical mechanism of the effects of IFN-alpha on the monoaminergic neurotransmitter system using an animal model (rats) [6].
• Locomotor activity of interferon-alpha-treated rats was significantly lower than that of control rats [7].

High impact information on Ifna1

• Streptozotocin induces the expression of interferon-alpha by pancreatic islets prior to the diabetes induced by streptozotocin [8].
• Islet expression of interferon-alpha precedes diabetes in both the BB rat and streptozotocin-treated mice [8].
• Southern analysis of the three cell lines revealed no consistent loss of loci for the interferon and c-jun genes, although early-passage clone 7 cells had one half the gene copy number for the interferon beta and c-jun genes and both early- and late-passage clone 7 cells lacked DNA sequences hybridizing with the probe for interferon alpha [9].
• In contrast, interferon-alpha/beta, tumor necrosis factor-alpha, interleukin-1 or -6, lipopolysaccharide and phorbol myristate acetate have no demonstrable effect [10].
• Rat ovarian surface epithelial cells transformed spontaneously in vitro have been found to have homozygous deletions of the interferon alpha (IFNA) gene [11].

Chemical compound and disease context of Ifna1

• Ribavirin, a guanosine analog, used in combination with interferon alpha (IFN-alpha) in the treatment of chronic hepatitis induced by hepatitis C virus (HCV) infection, has been shown to improve liver histology and to decrease transaminases even when administered alone [12].
• Adenovirus-mediated gene transfer of interferon alpha improves dimethylnitrosamine-induced liver cirrhosis in rat model [13].
• In vivo and in vitro glioma cell killing induced by an adenovirus expressing both cytosine deaminase and thymidine kinase and its association with interferon-alpha [14].
• RESULTS: Interferon alpha significantly decreased fibrosis in the CCl4 model only: area of fibrosis: 13.9+/-3.7 vs 10.5+/-3.3% (p<0.05), hydroxyproline: 1.8+/-0.6 vs 1.2+/-0.2 mg/g wet liver (p<0.001), respectively placebo vs interferon alpha [15].
• The purpose of this experimental study was to detect the effects of acetylsalicylic acid (ASA), vitamin E (Vit E), and interferon-alpha (IFN-alpha) on prevention of parenteral nutrition-associated cholestasis [16].

Biological context of Ifna1

• Gel mobility shift of the interferon gamma activation site/interferon alpha-stimulating response element was observed immediately after the aortic banding, whereas the band of sis-inducing element was shifted in the late stage at 60 minutes [17].
• Interferon alpha-induced apoptosis on rat preneoplastic liver is mediated by hepatocytic transforming growth factor beta(1) [18].
• In contrast, interferon-alpha and dexamethasone did not alter C1-esterase inhibitor gene expression [19].
• The decreased cell proliferation caused by IFN-alpha-induced IL-1beta may be responsible, at least in part, for IFN-alpha-induced depression.Neuropsychopharmacology (2006) 31, 2619-2626. doi:10.1038/sj.npp.1301137; published online 5 July 2006 [20].
• Immediately after the administration of IFN-alpha for 1 week, a decrease in the number of 5-bromo-deoxyuridine-labeled proliferating cells was observed in the DG; however, no effect was detected on the expression of mature neuronal phenotype in the newly formed cells 3 weeks later [20].

Anatomical context of Ifna1

• RESULTS: Interferon alpha induced leukocyte entrapment in retinal microcirculation and increased leukocyte adherence to the vessel walls [21].
• 4. In contrast, microinjection of interferon-alpha into the paraventricular nucleus of the hypothalamus (PVN) had no effect on splenic nerve activity, although an injection of glutamate increased the nerve activity [22].
• Also, an increase in the level of interleukin-1beta (IL-1beta), a major proinflammatory cytokine, was observed in the hippocampus following the administration of IFN-alpha [20].
• 1. We previously demonstrated that a central injection of interferon-alpha in rats induced a suppression of cytotoxicity of splenic natural killer cells which depended upon intact splenic sympathetic innervation, suggesting the important role of the splenic nerve in immunosuppression [23].
• Interferon-alpha and -gamma expression in the rat testis [24].

Associations of Ifna1 with chemical compounds

• METHODS: Normal MHC congenic rat strains that do not spontaneously develop diabetes or any other autoimmune syndrome were injected with the interferon-alpha inducer polyinosinic-polycytidylic acid (Poly IC) [25].
• RNA blotting analysis demonstrates that interferon-alpha (IFN-alpha) and its inducers, i.e. poly(I).poly(C), bacterial lipopolysaccharide (LPS) and tilorone (2,7-bis-[2-(diethylamino)ethoxy]fluoren-9-one), increase the expression of XD mRNA in liver [26].
• Poly(IC) induced interferon-alpha in C6 cells [27].
• Although high levels of interferon-alpha were produced by both intact and hypophysectomized rats, and the plasma corticosterone concentration increased dramatically in intact animals, corticosterone remained undetectable in hypophysectomized rats [28].
• Furthermore, the damage to cytochrome c oxidase was prevented by the putative interferon-alpha/beta receptor antagonist oxyphenylbutazone [29].

Regulatory relationships of Ifna1

• Blockade of nitric oxide synthase antagonized the interferon-alpha induced arginine vasopressin release from the amygdala but not from the hypothalamus [30].
• RESULTS: Rat interferon-beta and interferon-gamma significantly inhibited rat hepatic stellate cell proliferation while rat interferon-alpha did not affect the cell proliferation under the same culture condition [31].
• Prednisolone, platelet-activating factor receptor antagonist, or superoxide dismutase reduced leukocyte entrapment induced by interferon alpha in retinal microcirculation [21].
• It has been postulated that interferon-alpha (IFNalpha) decreases putrescine levels in regenerating liver by inhibiting ornithine decarboxylase (ODC) activity, the main enzyme in polyamine biosynthesis [32].
• We found that all four PPAR-alpha activators suppressed lipopolysaccharide-stimulated STAT1 phosphorylation and nuclear factor binding to gamma-interferon-activated sequence/interferon-alpha-stimulated response element sites known to contain STAT binding sites [33].

Other interactions of Ifna1

• From these findings it is concluded that the cytokines IL-1 beta, IFN-gamma and IFN-alpha act in a non-synergistic fashion in suppressing RINm5F cell proliferation and hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)[34]
• On the other hand, IFN-gamma and IFN-alpha both elicited marked decreases in proliferation and insulin content and secretion by the insulinoma cells [34].
• Using an immortalized astrocyte cell line (DITNC), we showed that lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) but not interferon-alpha (IFN-alpha) could individually induce secretory phospholipase A2 (sPLA2) mRNA and enzymatic activity [35].
• Effect of interferon-alpha on tyrosine hydroxylase and catecholamine levels in the brain of rats [7].
• Neuropeptide Y counteracts interferon-alpha-induced anorexia [36].

Analytical, diagnostic and therapeutic context of Ifna1

• Four groups (n = 26 each) of rats underwent resection and anastomosis of both ileum and colon: a control group and three groups receiving intraperitoneal 5-FU, interferon-alpha or both on the day of surgery and the next 2 days [37].
• The continuing search for effective adjuvant therapy after resection of intestinal malignancies has prompted a growing interest in both immediate post-operative regional chemotherapy and the combination of 5-fluorouracil (5-FU) and interferon-alpha as drugs of choice [37].
• To determine the exact locus of the IFN-alpha action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems [38].
• We first examined the concentrations of tetrahydrobiopterin (BH(4)) and monoamines in several regions of the brain after the intramuscular injection of IFN-alpha into rats; the levels of BH(4) and dopamine significantly decreased in the amygdala and raphe areas as compared with those of the controls [6].
• The effects of interferon-alpha/beta in a model of rat heart transplantation [39].

References