Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumonisin B(1) (FB(1)), a carcinogenic mycotoxin produced primarily by fungus Fusarium verticillioides in corn, causes several fatal animal diseases. In mice, liver is the primary site of its toxicity. Our previous study showed that maximum induction of interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) was observed at 4 and 8 h, respectively, after an acute po FB(1) treatment. To further investigate the time-related induction of other cytokines and genes involved in apoptosis signaling, male BALB/c mice were administered orally with either saline or 25 mg/kg of FB(1) and sampled 4 or 8 h after treatment. Expression of various genes was analyzed by ribonuclease protection assay. FB(1) treatment caused increased expression of TNFalpha and interleukin (IL)-1beta in both liver and kidney, whereas IL-1alpha and IL-1 receptor antagonist (IL-1Ra) expression was induced only in the liver. Expression of TNFalpha signaling molecules, TNF receptor 55 and receptor interacting protein, was increased in liver and kidney after FB(1) treatment. Caspase 8 expression was increased only in liver with no changes in kidney with FB(1). FB(1) treatment induced expression of Fas in liver and kidney with no alterations in Fas signaling molecules, Fas ligand, Fas-associated death domain and Fas-associated protein factor. Treatment of mice with FB(1) increased the expression of B-Myc, c-Myc and Max, oncogenic transcription factors in the kidney. FB(1) toxicity caused induction of cytokine network in liver with involvement of TNFalpha signaling pathway. Increased expression of caspase 8 involved in the TNFalpha signaling pathway may contribute to the apoptosis, whereas IL-1Ra induction could contribute to the proliferating effects observed in FB(1) toxicity.
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PMID:Fumonisin B(1)-induced alterations in cytokine expression and apoptosis signaling genes in mouse liver and kidney after an acute exposure. 1188 48

Although interferon (IFN)-beta is firmly established as a therapeutic agent for multiple sclerosis, information regarding its role in astrocyte cytokine production is limited. In primary cultures of human astrocytes, we determined the effects of IFN-beta on astrocyte cytokine [tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6] and inducible nitric oxide synthase (iNOS) expression by ribonuclease protection assay and ELISA. We found that IFN-beta inhibited astrocyte cytokine/iNOS induced by IL-1 plus IFN-gamma, but in the absence of IFN-gamma, IFN-beta enhanced IL-1-induced cytokine/iNOS expression. Electrophoretic mobility shift analysis (EMSA) demonstrated that IFN-gamma induced sustained IFN-gamma-activated sequence (GAS) binding, while IFN-beta induced transient GAS binding. When used together, IFN-beta inhibited IFN-gamma-induced GAS binding activity. Nuclear factor-kappa B (NF-kappaB) activation was not altered by either IFNs, whereas IFN stimulated response element (ISRE) was only activated by IFN-beta and not IFN-gamma. These results suggest that IFN-beta can both mimic and antagonize the effect of IFN-gamma by modulating induction of nuclear GAS binding activity. Our results demonstrating differential regulation of astrocyte cytokine/iNOS induction by IFN-beta are novel and have implications for inflammatory diseases of the human CNS.
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PMID:Modulation of astrocyte inducible nitric oxide synthase and cytokine expression by interferon beta is associated with induction and inhibition of interferon gamma-activated sequence binding activity. 1243 83

Endotoxin [lipopolysaccharide (LPS)] from Gram-negative bacteria is found in amniotic fluid in intrauterine infections that associate with the risk for spontaneous premature birth, bronchopulmonary dysplasia (BPD), and respiratory distress syndrome. Toll-like receptor 4 (TLR4) is the signaling receptor for LPS. The aim was to investigate the primary inflammatory response in mice shortly after administration of LPS to the dam (14 and 17 d of pregnancy), to the newborn, or into the amniotic fluid. The expression levels of TLR4, IL-1, tumor necrosis factor-alpha, IL-6, IL-10, macrophage inflammatory protein-2, and IL-1 receptor 1 were studied with ribonuclease protection assay. In addition, TLR4 protein was analyzed with Western blotting. The fetal membranes expressed TLR4 mRNA and protein and showed an acute cytokine response to LPS when LPS was administrated into the amniotic fluid. There was distinct ontogeny in the responsiveness of fetal lung to LPS: on fetal day 14 (term 20 d), both the expression of TLR4 and the acute cytokine response were undetectable 5 h after LPS; they became detectable by fetal day 17. TLR4 and the cytokine response further increased after birth. In maternal lung, the TLR4 expression was strongest and up-regulated in parallel with the induction of the cytokines. We propose that TLR4 controls the magnitude of the LPS-induced cytokine response during the perinatal period.
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PMID:Expression of toll-like receptor 4 and endotoxin responsiveness in mice during perinatal period. 1571 65

The host response during resolution of Pneumocystis murina infection following withdrawal of Dexamethasone (Dex) induced immunosuppression was analyzed. Mice were inoculated with P. murina and treated with Dex for 4 weeks. Treatment was stopped and mice were sacrificed at d1, d7, and d14. Control mice were treated in the same manner, but were inoculated with nonviable P. murina. P. murina was actively cleared from the lungs following withdrawal of Dex treatment. No P. murina was detected in control mice. Significantly more neutrophils, lymphocytes, macrophages, and eosinophils were recovered from the lungs of mice that had been infected with P. murina than from control mice at d7, but only neutrophils remained significantly elevated at d14. Significantly more CD4+ and CD8+ T cells were purified from the lungs of mice that had been infected with P. murina mice at d7 and d14. Cytokine levels were measured in lung lavage fluid by ELISA. TNF-alpha, IFN-gamma, IL-1, and IL-6 levels were higher in mice that had been inoculated with P. murina at all three time points. TNF-alpha and IL-1 levels did not change significantly following withdrawal of Dex treatment. Low levels of IL 6 were detected at d1, but increased significantly by d7 and d14. IFN-gamma levels peaked at d14. Chemokine message levels were measured in lung tissue by ribonuclease protection assay. MIP-1beta and IP-10 message increased between d1 and d7 and then decreased by d14. RANTES message levels increased from d1 to d7 and remained elevated at d14. Withdrawal of Dex induced immunosuppression from P. murina infected mice resulted in activation of many arms of the host response that lead to resolution of the infection.
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PMID:Resolution of Pneumocystis murina infection following withdrawal of corticosteroid induced immunosuppression. 1632 97

Neurocysticercosis is a parasitic infection of the human central nervous system caused by the cestode Taenia solium. The most common clinical manifestations of neurocysticercosis are seizures. Taenia crassiceps cysticercosis in mice has been used as an experimental model for T. solium cysticercosis. Granulomas surrounding murine cysticerci have striking immunopathological resemblance to human neurocysticercosis; early stage granulomas were able to induce seizures in a rodent model. To assess the role of proinflammatory cytokines in early stage granulomas, we isolated RNA from murine cysticercal granulomas and checked for cytokine expression by reverse transcriptase-polymerase chain reaction (RT-PCR) and/or ribonuclease (RNase) protection assays. Cytokine expression was compared with histological stages. Interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, and tumor necrosis factor (TNF-alpha) were the major cytokines detected in all granulomas. Signals for IL-12, IL-18, and IL-6 RNA were not consistently detected and, when detected, were barely demonstrable. Expression of migration inhibitory factor (MIF), IL-6, IL-1alpha, TNF-alpha, and IL-18 was not significantly different between early and late-stage granulomas. Expression of IL-1beta, IL-1 receptor antagonist, and IL-12 p40 were higher in late, compared with early, stages. Thus, we demonstrated a broad range of cytokines in these granulomas. However, we did not document preferential expression of any proinflammatory cytokines in early stage granulomas. Thus, proinflammatory cytokines are not responsible for the seizures in the rodent model of neurocysticercosis.
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PMID:Proinflammatory cytokines in granulomas associated with murine cysticercosis are not the cause of seizures. 1699 90

The effect of exogenous RNA on many cellular functions has been studied in a variety of eukaryotic cells but there are few reports on macrophages. In the present study, it is demonstrated that cytoplasmatic RNA extracted from rat macrophages stimulated with Escherichia coli lipopolysaccharide (LPS), referred to as L-RNA, induced the release of TNF-alpha and IL-1 from monolayers of peritoneal resident macrophages. The activity of L-RNA was not altered by polymyxin B but was abolished by ribonuclease (RNase) pretreatment, indicating the absence of LPS contamination and that the integrity of the polynucleotide chain is essential for this activity. Both the poly A(-) and poly A(+) fractions obtained from L-RNA applied to oligo(dT)-cellulose chromatography induced TNF-alpha and IL-1 release. The L-RNA-induced cytokine release was inhibited by dexamethasone and seemed to be dependent on protein synthesis since this effect was abolished by cycloheximide or actinomycin-D. The LPS-stimulated macrophages, when pre-incubated with [5-(3)H]-uridine, secreted a trichloroacetic acid (TCA) precipitable material which was sensitive to RNase and KOH hydrolysis, suggesting that the material is RNA. This substance was also released from macrophage monolayers stimulated with IL-1beta but not with TNF-alpha, IL-6 or IL-8. The substance secreted ((3)H-RNA) sediments in the 4-5S region of a 5-20% sucrose gradient. These results show that L-RNA induces cytokine secretion by macrophage monolayers and support the idea that, during inflammation, stimulated macrophages could release RNA which may further induce the release of cytokines by the resident cell population.
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PMID:RNA from LPS-stirnulated macrophages induces the release of tumour necrosis factor-alpha and interleukin-1 by resident macrophages. 1847 60

Interleukin-1beta (IL-1beta) has been implicated in various neuropathologies, while IL-1 receptor antagonist (IL-1ra) has been shown to reduce neuronal injury. We investigated the pattern of expression of both cytokines in murine hippocampus after trimethyltin (TMT) intoxication. Using a ribonuclease protection assay, we demonstrated induction of transcription of IL-1beta and IL-1ra 3 days following TMT treatment which correlated with the peak of neuronal apoptosis. At this time, immunocytochemical staining revealed enhanced expression of both cytokines in NG2 proteoglycan expressing ameboid cells located at the site of neurotoxic insult, some of which bound also the microglial marker, lectin. There was some overlap between NG2 and lectin staining. Our results suggest that the two cytokines are involved in apoptotic processes in dentate granule cells and indicate that the pro-apoptotic effect of IL-1beta prevails over the presumed protective action of IL-1ra. The novel finding of expression of both cytokines in NG2(+) cells of ameboid phenotype indicates that these cells, through the regulatory roles of pro- and anti-inflammatory cytokines, may be involved in control of neuronal death or survival after injury.
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PMID:Trimethyltin-evoked apoptosis of murine hippocampal granule neurons is accompanied by the expression of interleukin-1beta and interleukin-1 receptor antagonist in cells of ameboid phenotype, the majority of which are NG2-positive. 1863 41


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