Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.27.5 (RNase)
17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription factor NF-kappaB is essential for the induction of nitric oxide synthase (NOS) II (iNOS) by bacterial lipopolysaccharide in murine macrophages (Xie, Q. W., Kashiwabara, Y., and Nathan, C. (1994) J. Biol. Chem. 269, 4705-4708). In 3T3 fibroblasts, agents other than cytokines are efficacious inducers of NOS II expression. In addition to cytokines such as interferon-gamma or tumor necrosis factor-alpha, protein kinase C-stimulating agents such as tetradecanoylphorbol-13-acetate, or cyclic AMP-elevating agents such as forskolin and 8-bromo-cAMP markedly increased NOS II mRNA (measured by Sl nuclease and RNase protection analyses), NOS II protein (determined by Western blotting), and NOS activity (measured by chemiluminescence detection of NO2-). Transforming growth factor-beta1 (which is an inhibitor of NOS II induction in other cell types) potentiated NOS II mRNA expression produced by all inducing agents listed, whereas dexamethasone, pyrrolidine dithiocarbamate and 3,4-dichloroisocoumarin (inhibitors of NF-kappaB activation) suppressed NOS II mRNA induction in response to all stimulants. In electrophoretic mobility shift assays, nuclear protein extracts from 3T3 cells stimulated with any of the inducing agents significantly slowed the migration of an NF-kappaB-binding oligonucleotide, whereas nuclear extracts from untreated control cells did not. These experiments indicate that NF-kappaB is the key control element for the induction of NOS II in response to at least three different second messenger pathways in 3T3 cells.
...
PMID:In murine 3T3 fibroblasts, different second messenger pathways resulting in the induction of NO synthase II (iNOS) converge in the activation of transcription factor NF-kappaB. 862 88

During the Spacelab Life Sciences-2 mission, rats were dissected in space and biosamples were returned to Earth for analysis. Immunologic studies addressed the kinetics of T lymphocyte proliferative responses, cytotoxic activity of natural killer cells, and cytokine production. Experiments were performed by using spleen and bone marrow of rats dissected before flight, during flight, immediately after landing of the space shuttle (R + 0), or 14 days after landing (R + 14), as well as those of respective control animals. Each group consisted of five male Sprague-Dawley rats. It was demonstrated that T lymphocyte activity of rats dissected in flight was significantly decreased compared with the controls. This was observed during 48-, 72-, and 96-h cultivation and stimulation with the following mitogenic stimuli: concanavalin A (Con A; 0.1, 1.0, and 10.0 mg/ml), phytohemagglutinin (PHA; 2.5 mg/ml), and interleukin-2 (IL-2; 1 U/ml). The cell proliferation rate in rats dissected immediately after landing did not decrease, whereas that in rats dissected at R + 14 increased. The activity of spleen natural killer cells was reduced in response to 51Cr-labeled target cells during flight (YAC-1 and K-562) and after flight (YAC-1). At R + 14, their activity returned to normal. Another technique employed to measure natural cytotoxicity, using [3H]uridine-labeled target cells and ribonuclease, did not reveal any differences between control and experimental groups. In bone marrow, the activity of natural killer cells did not vary significantly. The production of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, and TNF-beta in spleen cell cultures of the flight rats was reduced. At R + 0, IL-1 and TNF-beta levels remained lowered, whereas TNF-alpha was increased. At R + 0, interferon-alpha and interferon-gamma levels were diminished. In summary, cell-mediated immunity in rats was significantly suppressed during flight. The time course variation of immune parameters after flight suggests that the changes may truly indicate a response of the immune system to spaceflight conditions that could increase over time.
...
PMID:Effect of SLS-2 spaceflight on immunologic parameters of rats. 882 61

90K is a secreted glycoprotein with tumor suppressive functions, which is up-regulated in various types of cancer and in AIDS. In order to understand the regulation of its expression, the mouse 90K gene was isolated and analyzed. The gene spans about 8.8-kilobase pairs and consists of 6 exons and was localized on chromosome 11, region E. RNase protection identified one major transcription start site (+1) and three minor ones (-3, +32, +34). The mouse 90K gene was found to have a TATA-less promoter of unusual structure. The 2. 3-kilobase pair 5'-flanking region exhibited strong promoter activity in NIH 3T3 cells; however, it contained neither a TATA-box nor a SP1 site and was not GC-rich. No known initiator motif was found around the transcription start site. 5'- and 3'-deletions defined a minimal promoter of 51 base pairs (-66 --> -16), not including the start site, essential and sufficient for promoter activity. This minimal promoter showed increased activity after stimulation with interferon-gamma or poly(I.C), a substance mimicking viral infection. Essential for both inductions was the integrity of an interferon regulatory factor element within this sequence, a potential binding site for the anti-oncogenic transcription factor interferon regulatory factor-1.
...
PMID:Expression of the 90K immunostimulator gene is controlled by a promoter with unique features. 901 22

The signalling mechanisms that regulate epidermal permeability barrier homeostasis are not known. Previous Northern blot analysis showed that both acute and chronic barrier disruption increase mRNA levels of several cytokines in murine epidermis. To further characterize the epidermal response to barrier abrogation, we used more sensitive, multi-probe RNase protection assays to measure the mRNA levels of additional cytokines, as well as cytokine receptors in acute and chronic models of barrier disruption. Normal mouse epidermis expressed interleukin (IL)-1 alpha, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and IL-6 mRNAs. Following tape-stripping, only the mRNA levels for TNF-alpha, IL-1 alpha, IL-1 beta and IL-6 increased at 2.5 and 7 h, and returned toward normal levels by 18 h. No mRNAs encoding TNF-beta, IL-2, IL-3, IL-4 or IL-5, were detected in the epidermis either under basal conditions or after tape-stripping. Similarly, in a chronic model, essential fatty acid deficiency, epidermal levels of TNF-alpha, IL-1 alpha, IL-1 beta and IL-6 mRNAs, but not IFN-gamma mRNA, were elevated over controls; and again, mRNAs for the remaining probed cytokines were not detected. In contrast, in the dermis, only IL-1 beta mRNA levels increased 2.5 h after tape-stripping, and remained elevated at 18 h. mRNAs encoding the IL-1 (p60), IFN-gamma and IL-6 receptors were present in epidermis, but their levels remained unchanged following either acute or chronic barrier disruption. In contrast, epidermal TNF (p55) receptor mRNA levels were increased by 87% (P < 0.01) at 2.5 h, returned to control levels at 7 h and were increased by 68% (P < 0.03) at 18 h after tape-stripping. The increase at 2 h was confirmed by Northern blot analysis and was not prevented by latex occlusion performed immediately after tape-stripping mRNAs for the IL-1 (p80) receptor and TNF (p75) receptor were not detected in epidermis. Low levels of TNF (p55) receptor mRNA were present in the dermis, and they remained unchanged after tape-stripping. The presence of specific receptor mRNAs in the epidermis and dermis suggests that these tissues are capable of responding in an autocrine and/or paracrine fashion to the cognate cytokines. These results suggest that epidermal cytokines produced after barrier disruption may initiate a cytokine cascade which could regulate cytokine and cytokine receptor production and/or inflammatory responses.
...
PMID:Barrier disruption increases gene expression of cytokines and the 55 kD TNF receptor in murine skin. 920 92

Trophoblast cells do not normally express major histocompatibility complex (MHC) class II antigens during placental development in either mice or rats. We have previously observed that in vivo treatment of pregnant mice with interferon-gamma (IFN gamma) induces immunohistochemically detectable class II cell surface expression in many maternal cell types, but not on placental cells or other cells of extra-embryonic origin. Both IFN gamma- and 5-azacytidine-induced placental class II expression have been reported in mice by other scientists, however, which made it important to further clarify this issue. The present study was performed to analyze whether treatment of pregnant mice with recombinant IFN gamma or the drug 5-azacytidine in vivo can induce detectable MHC class II Ab mRNA expression. A strain of transgenic mice carrying a cytomegalovirus-regulated MHC class II Abq transgene, which was strongly expressed in the placenta, was used as a positive control in all in situ hybridizations and ribonuclease protection analyses. All mice were analyzed on gestation Days 12.5 and 17.5. Treatment of pregnant mice with IFN gamma did not induce detectable class II expression in the placental cells, whereas the maternal decidua showed expression both at the mRNA and protein level. Similarly, treatment with 5-azacytidine did not induce class II expression in the placenta, while a slight increase in mRNA expression was detected in the maternal decidual and uterine tissues. These results strengthen the opinion that MHC class II mRNA cannot normally be induced in murine placental cells after IFN gamma or 5-azacytidine treatments.
...
PMID:Lack of detectable major histocompatibility complex class II a beta-chain messenger ribonucleic acid in placentas of interferon-gamma- and 5-azacytidine-treated mice. 931 71

Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults. However, the mechanisms of increased neonatal tolerance are unknown, as are the cell types that contribute to oxygen resistance. This study examined hyperoxic lung injury in neonatal and adult C57BL/6 mice. Adults and neonatal mice were exposed to > 95% oxygen for 78 h and 10 days, respectively. Lung mRNAs were assayed by RNase protection assay. After 72 h of exposure, the messages encoding tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta and 6 (IL-1 beta, IL-6) were increased 2-fold in adult lungs. However, at this time point these mice are near or at lethality. No alterations in neonatal lung mRNAs were detected until 7 days of oxygen exposure. At that time neonatal mice demonstrated increases in lung mRNAs encoding TNF-alpha, IL-1 beta, and IL-6 of 3-, 5-, and 8-fold, respectively. Acute alveolitis and slight edema were detected, but lethality wasn't observed until 10 days of exposure. In situ hybridization in neonatal mice suggests accumulation of TNF-alpha and IL-1 beta transcripts in pulmonary interstitial macrophages and in a subset of neutrophils after 7 days of exposure. Messages encoding IL-1 alpha, IL-2, IL-3, IL-4, IL-5,IL-10 interferon-gamma (IFN-gamma), and TNF-beta were not altered from controls in either adult or neonatal mice at any time point examined. In conclusion, adult mice demonstrate little change in cytokine mRNA until lethality is imminent, whereas newborn mice demonstrate an acute induction of TNF-alpha, IL-1 beta, and IL-6 early in the development of hyperoxic injury, which suggests that a rapid cytokine response early in the development of hyperoxic injury may play an important role in the adaptation of neonatal lungs to toxicity from prolonged oxygen exposure.
...
PMID:Comparison of adult and newborn pulmonary cytokine mRNA expression after hyperoxia. 935 35

Nitric oxide (NO) plays an important role in cellular signaling and host defense, and it also contributes to the deleterious effects of immune response. Until recently, the lack of specific inhibitors of various forms of nitric oxide synthase (NOS) hampered a stringent evaluation of the role played by inducible NOS (iNOS) in cell damage. The present study investigated the use of antisense oligodeoxynucleotides (AS-ODNs) to selectively inhibit the expression of iNOS. AS-ODNs (1-10 microM) inhibited, in a time-dependent and dose-dependent manner, iNOS activity in RAW 264.7 murine macrophages. Maximal inhibitory effect was >90%, and control ODNs had little or no effect on NO production. Treatment with AS-ODNs decreased iNOS protein and mRNA level in studied cell, and control ODNs again were ineffective. The decreased levels of the target mRNA in AS-ODN-treated samples suggest that the AS-ODNs used act as substrates for ribonuclease (RNase) H. Lipofection enhanced the effect of AS-ODNs on iNOS activity. However, this potentiation appears to be different from the antisense effect, in which the AS-ODNs studied were involved. Liposaccharide/interferon-gamma (LPS/IFN-gamma) induced iNOS, and increased NO production impaired the viability of macrophages. Treatment of RAW 264.7 cells with 10 microM AS-ODNs prevented the NO-induced lethal cell damage.
...
PMID:The effect of antisense oligodeoxynucleotides on nitric oxide secretion from macrophage-like cells. 945 Sep 10

Interleukin-12 (IL-12) production by human monocytes is stringently regulated through the inducibility of both subunits, p35 and p40, and expression of p35 mRNA is the limiting factor for the secretion of the bioactive IL-12 p70 heterodimer. Optimal induction of p35 mRNA requires priming of the monocytes by interferon-gamma (IFN-gamma), followed by brief exposure to lipopolysaccharide or other bacterial products. To investigate control of p35 gene expression, we isolated genomic clones containing the human p35 gene and determined the 5' end of the mRNA expressed in monocytes. We discovered that a unique p35 transcript is induced in monocytes that begins downstream of a consensus TATA box that lies within the 5' end of the cDNA originally cloned from Epstein-Barr virus (EBV)-transformed B cells. Analysis of p35 mRNA by Northern blotting showed that the message from monocytes is approximately 200 bases shorter than message derived from the EBV-transformed B-cell line VDS. The initiation sites downstream from the TATA box were confirmed by RNase protection and 5' RACE. The data indicate that p35 transcription can initiate from different sites depending on the cell type and that the shorter inducible transcript in monocytes is the one that accumulates after stimulation. Protein translation of these two forms may result in proteins of different sizes with potential implications for the regulation of IL-12 secretion and function.
...
PMID:Interferon-gamma-dependent inducible expression of the human interleukin-12 p35 gene in monocytes initiates from a TATA-containing promoter distinct from the CpG-rich promoter active in Epstein-Barr virus-transformed lymphoblastoid cells. 961 61

The objective of this study was to investigate the impact of feeding mice a diet rich in n-3 polyunsaturated fatty acids (PUFA) from fish oil on the interleukin-12 (IL-12) and interferon-gamma (IFNgamma) production during the early stage of an infectious challenge with Listeria monocytogenes. Weanling female C3H/HeN mice were fed AIN-93G experimental diets containing 20%, by weight one of three fat sources: lard (low PUFA), soybean oil (n-6 PUFA) or a mixture (9:1) of menhaden fish oil and corn oil (n-3 PUFA). After 4 weeks, mice were injected intraperitoneally with 10(5) Listeria monocytogenes and the concentration of IL-12(p70) and IFNgamma in serum was determined 24 h post-infection by ELISA. IL-12p35, IL-12p40 mRNA, and IFNgamma mRNA in the spleen were quantified by RNase protection assay. The number of IFNgamma-producing cells in the spleen was determined by flow cytometry using an intracellular staining procedure. We found that n-3 PUFA-fed mice had lower levels of circulating IL-12 at 24 h post-infection than n-6 PUFA- or low PUFA-fed mice (9.7+/-3.4 pg/ml vs. 61.6+/-10.6, and 44.4+/-12.5 pg/ml, respectively; P=0.002, n = 10/trt). The level of IL-12 p35 mRNA did not significantly differ among dietary treatment groups. However, IL-12p40 mRNA was significantly lower in n-3 PUFA- and n-6 PUFA-fed mice compared to low-PUFA-fed mice. Further, the n-3 PUFA group also had the lowest circulating IFNgamma (4.4+/-1.8 ng/ml vs. 9.1+/-1.0, and 9.7+/-2.1 ng/ml, respectively; P = 0.007. n = 8-10/trt). The n-3 PUFA-fed mice had significantly lower IFNgamma mRNA in their spleens compared to the mice fed the other fat sources. In agreement with having lower circulating IFNgamma and lower splenic IFNgamma mRNA, n-3 PUFA-fed mice had a significantly lower percentage of IFNgamma-producing cells in their spleens compared with the n-6 PUFA-fed group (2.1+/-0.6 vs. 4.2+/-0.7%; P = 0.037, n = 10/trt). In summary, feeding mice a diet rich in n-3 PUFA from fish oil significantly lowered the production of both IL-12 and IFNgamma during the early phase of a Listeria infection.
...
PMID:Dietary omega-3 polyunsaturated fatty acids from fish oil reduce interleukin-12 and interferon-gamma production in mice. 1006 39

Bone marrow-culture-derived macrophages activated with interferon-gamma and lipopolysaccharide produced less nitric oxide (NO) when cultured with vesicular stomatitis virus (VSV)-infected BALB/c3T3 (3T3-VSV) than macrophages activated in an identical manner and cultured alone, with uninfected BALB/c3T3 (3T3), or with P815. However, all four groups of macrophages produced nearly the same amount of interleukin-6 (IL-6). Addition of VSV to activated macrophages did not change the amount of NO produced. The amount of NO generated by two non-macrophage sources of NO was not affected by the presence of either P815 or 3T3-VSV. Reverse transcriptase-polymerase chain reaction showed a decrease in the amount of inducible nitric oxide synthase (iNOS) but not IL-6 mRNA from macrophages cocultured with 3T3-VSV compared with macrophages cocultured with P815. The reduction in iNOS mRNA was confirmed by ribonuclease protection assay. When RAW 264.7 transfected with an iNOS regulatory construct were activated and incubated with 3T3-VSV there was a decrease in the expression of the reporter luciferase gene and NO production but not IL-6 production compared with cells incubated with either medium alone or with P815.
...
PMID:Interaction with vesicular stomatitis virus-infected BALB/c3T3 cells inhibits the synthesis of nitric oxide in activated murine bone marrow culture-derived macrophages. 1033 88


<< Previous 1 2 3 4 5 6 Next >>

---