Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rana catesbeiana ribonuclease (RC-RNase) possesses tumor-specific cytotoxicity, which can be synergized by IFN-gamma. However, it is unclear how RC-RNase and RC-RNase/IFN-gamma induce cell death. In this study, we use substrate cleavage assays to systematically investigate RC-RNase- and RC-RNase/IFN-gamma-induced caspase activation in HL-60, MCF-7, and SK-Hep-1 cells. We find that RC-RNase and RC-RNase/IFN-gamma induce mitochondria-mediated caspase activation in HL-60 and MCF-7 cells but not in SK-Hep-1 cells, although death of SK-Hep-1 cells is closely related to mitochondrial disruptions. Our findings provide evidence that RC-RNase and RC-RNase/IFN-gamma can kill different cancer cells by distinct mechanisms. Compared with onconase, RC-RNase seems to harbor a more specific anti-cancer activity.
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PMID:Synergism of Rana catesbeiana ribonuclease and IFN-gamma triggers distinct death machineries in different human cancer cells. 1562 Jul 24

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

ISG20 is an ribonuclease specific for single-stranded RNA and considered to play a role in innate immunity against virus infections. We herein show that both poly IC, an authentic double-stranded RNA, and IFN-gamma induced ISG20 expression in cultured HUVEC. Poly IC-induced ISG20 expression was inhibited by LY294002, an inhibitor of PI3K, or by RNA interference against IFN regulatory factor three. ISG20 expression was not induced by IFN-beta, loxoribine or CpG oligonucleotide. These results suggest that ISG20 induction by poly IC may not be dependent on the IRF-3-mediated type I IFN induction pathway in HUVEC. ISG20 may be involved in innate immunity against viral infection in vascular endothelial cells.
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PMID:Expression of interferon-stimulated gene 20 in vascular endothelial cells. 1835 10

Chemical respiratory allergy is an important occupational health problem, but there are currently available no validated methods for hazard identification. There has been interest for some time in the application of cytokine profiling for the characterization of chemical allergens. We have now examined whether these cytokine expression patterns are regulated at the level of mRNA and/or protein production. Mice (BALB/c strain) were exposed topically to the contact allergen 2,4-dinitrochlorobenzene (DNCB), or to the respiratory allergen trimellitic anhydride (TMA). Thirteen days after the initiation of exposure, a single cell suspension of draining (auricular) lymph node cells (LNC) was prepared. Cells were cultured for 24-120h and supernatants analyzed for cytokine protein by cytokine bead array. In parallel experiments total RNA was prepared from freshly isolated or cultured cells and cytokine gene expression was analyzed by ribonuclease protection assay (RPA) or by real time reverse transcription-polymerase chain reaction (RT-PCR). DNCB-activated LNC secreted high levels of the type 1 cytokines interferon (IFN)-gamma and IL-12 compared with TMA-stimulated LNC. The converse type 2 pattern was observed following treatment with TMA. Freshly isolated LNC from TMA-treated mice displayed a selective type 2 cytokine mRNA profile as measured by RPA. In contrast, RNA isolated from DNCB-activated LNC displayed a more mixed cytokine phenotype with relatively low levels of transcripts for both type 1 and type 2 cell products. When cytokine gene expression was measured by the more sensitive real time RT-PCR technique, more vigorous expression of IL-4 was recorded for TMA-activated LNC compared with DNCB-activated LNC but there was no evidence for elevated IFN-gamma transcripts for the latter treatment. The observation that IFN-gamma mRNA expression is not increased in DNCB-activated LNC despite robust secretion of this cytokine indicates that production is controlled mainly at the level of translation of previously transcribed mRNA or of protein secretion. Furthermore, the preferential cytokine profile recorded following TMA exposure was more clearly contrasting when measured at the level of protein secretion rather than at the level of mRNA expression. Experience to date suggests that the measurement of induced cytokine profiles shows promise for the hazard identification and characterization of chemical respiratory allergens, and that the end point best suited for this purpose is cytokine secretion rather than mRNA expression.
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PMID:Cytokine profiling of chemical allergens in mice: measurement of message versus protein. 1870 16


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