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

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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)

One of the consequences of cytokine-orchestrated inflammation after CNS trauma is apoptosis. Our hypothesis is that cell death in the spinal cord after injury results in part from increased synthesis and release of IL-1beta. Using a ribonuclease protection assay, we demonstrated that there is increased transient expression of IL-1beta mRNA and, by using IL-1beta protein ELISA assay, that there are increased IL-1beta protein levels in the contused rat spinal cord, initially localized to the impact region of the spinal cord (segment T8). Using an ELISA cell death assay, we showed that there is apoptosis in the spinal cord 72 h after injury, a finding that was confirmed by measuring caspase-3 activity, which also significantly increased at the site of injury 72 h after trauma. Treatment of the contused spinal cord at the site of injury with the IL-1 receptor antagonist (rmIL-lra, 750 ng/mL) for 72 h using an osmotic minipump completely abolished the increases in contusion-induced apoptosis and caspase-3 activity.
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PMID:IL-1 receptor antagonist prevents apoptosis and caspase-3 activation after spinal cord injury. 1156 5

The present study was designed to determine cytokines produced by primary human bronchial epithelial cells (HBECs) exposed to ambient air pollution particles (EHC-93). Cytokine messenger RNA (mRNA) was measured using a ribonuclease protection assay and cytokine protein production by enzyme-linked immunosorbent assay. Primary HBECs were freshly isolated from operated lung, cultured to confluence, and exposed to 10 to 500 microg/ml of a suspension of ambient particulate matter with a diameter of less than 10 microm (PM(10)) for 2, 8, and 24 h. The mRNA levels of leukemia inhibitory factor (LIF), granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1alpha, and IL-8 were increased after exposure to PM(10), and this increase was dose-dependent between 100 (P < 0.05) and 500 (P < 0.05) microg/ml of PM(10) exposure. The concentrations of LIF, GM-CSF, IL-1beta, and IL-8 protein measured in the supernatant collected at 24 h increased in a dose- dependent manner and were significantly higher than those in the control nonexposed cells. The soluble fraction of the PM(10) (100 microg/ml) did not increase these cytokine mRNA levels compared with control values and were significantly lower compared with HBECs exposed to 100 microg/ml of PM(10) (LIF, IL-8, and IL-1beta; P < 0.05), except for GM-CSF mRNA (P = not significant). We conclude that primary HBECs exposed to ambient PM(10) produce proinflammatory mediators that contribute to the local and systemic inflammatory response, and we speculate that these mediators may have a role in the pathogenesis of cardiopulmonary disease associated with particulate air pollution.
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PMID:Particulate matter induces cytokine expression in human bronchial epithelial cells. 1158 2

PRL has been reported to regulate fat metabolism in several species. We recently reported PRL receptor (PRLR) expression in mouse adipocytes and increased levels of PRLR expression in the adipose tissue of lactating and PRL-transgenic mice compared with controls. These results suggest PRLR-mediated effects in adipose tissue. However, to date most studies have been performed in vivo, and it is unclear whether PRL has direct effects on adipocytes. The PRLR belongs to the cytokine receptor family, and a family of suppressors of cytokine signaling (SOCS) was recently identified. The present study was performed to investigate whether PRL has direct effects on adipocytes. The expression of cytokine-inducible SH2-domain-containing protein (CIS), SOCS-3, and SOCS-2 mRNA and protein was analyzed using ribonuclease protection assay and immunoblotting, respectively. Ovine PRL induced CIS mRNA expression and a combination of oPRL and insulin induced SOCS-3 mRNA expression in adipocytes cultured in vitro for 0-240 min, demonstrating PRLR-mediated direct effects in these cells. Furthermore, CIS, SOCS-3, and SOCS-2 mRNA and protein were all transiently expressed in adipose tissue obtained from female mice stimulated with oPRL (1 microg/g BW) for 0-24 h. In adipose tissue of female mice with endogenously high PRL levels, PRL-transgenic mice, only SOCS-2 expression was increased. The level of SOCS-2 mRNA was also increased in adipose tissue during pregnancy and lactation compared with that in wild-type virgin female mice. A possible reason for increased SOCS-2 expression after prolonged PRL exposure during lactation and in the PRL transgenes could be to restore the sensitivity of adipose tissue to PRL. In addition, the direct effect of PRL on leptin production was investigated in adipocytes cultured in vitro for 6 h. PRL inhibited insulin-induced leptin production in vitro. However, PRL had no effect on leptin production in the absence of insulin. In contrast, serum leptin concentrations were increased in PRL-transgenic females compared with control mice. In conclusion, our results demonstrate functional PRLRs in mouse adipocytes and suggest a role for CIS, SOCS-3, and SOCS-2 in regulating PRL signal transduction in adipose tissue.
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PMID:PRL receptor-mediated effects in female mouse adipocytes: PRL induces suppressors of cytokine signaling expression and suppresses insulin-induced leptin production in adipocytes in vitro. 1160 56

Symptoms of nasal, pharyngeal and ocular discomfort have been reported among workers in the wood surface-coating industry. Symptoms were reported more often by workers using ultraviolet radiation-curable acrylate coatings (UV coatings), which contain potential chemical sensitizers, than by those using acid-curing coatings. Furthermore, increased levels of eosinophil cationic protein (ECP) and albumin, but not tryptase, in nasal lavage from workers exposed to UV coatings have been observed. To further examine whether air contaminants present in the UV-coating industry are causing the observed increase in symptoms, the inflammatory process in the nasal mucosa of workers exposed to UV coatings was investigated. Clinical and biochemical endpoints were selected to distinguish between specific and non-specific hypersensitivity and to test the hypothesis that the symptoms were consistent with Type IV hypersensitivity. The nasal lavage and nasal biopsy were performed under local anesthetic at the workplace during working hours after a minimum of 2 h of work in both the exposed and control groups. Albumin and ECP, and the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8), were used as inflammatory markers. A multi-probe ribonuclease protection assay was used to attempt to detect cytokine variation in human nasal biopsies. The cytokine genes analyzed were TNF-alpha, GM-CSF, interferon-gamma, IL-2, IL-4 and IL-5. L32 and GAPDH were used as control genes for mRNA expression levels. Mucosal inflammation symptoms correlated with increased levels of albumin, but not with increased levels of ECP, secreted proinflammatory cytokines or cytokine gene mRNA expression. We conclude that the symptoms are non-specific and do not correlate with occupational exposure to UV coatings under the conditions of this investigation.
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PMID:Absence of proinflammatory cytokine gene expression in nasal biopsies from wood surface-coating industry workers. 1167 74

Cytokines play an important and complex role in the pathogenesis of systemic autoimmune diseases. In susceptible H-2s mice, inorganic mercury (Hg) induces lymphoproliferation, antinucleolar antibodies against the 34-kDa-protein fibrillarin, and systemic immune-complex (IC) deposits. Here, we report extensive analysis of cytokine mRNA levels in susceptible A.SW (H-2s) and resistant A.TL (H-2tl) mice under unstimulated conditions and during oral treatment with Hg and/or silver nitrate (Ag). Cytokine mRNA expression in lymphoid tissues was assessed using the ribonuclease protection assay and phosphorimaging. Baseline expression of IL-2 and IFN-gamma mRNA was higher in A.SW than in A.TL mice. In A.SW mice, Hg treatment caused early up-regulation of IL-2 and IFN-gamma levels, followed by substantial expression of IL-4 mRNA, which was significant compared to control A.SW and Hg-treated A.TL mice. Hg-exposed A.TL mice exhibited unchanged IFN-gamma, reduced IL-2 and greatly increased IL-10 mRNA expression. Ag-treated A.SW mice, which develop antifibrillarin antibodies (AFA) but exhibit minimal immune activation and no IC deposits, showed an early increase in IL-2 and IFN-gamma mRNA, but only a small and delayed rise in IL-4 mRNA. In conclusion, H-2-linked resistance to Hg-induced AFA is characterized by low constitutive expression of IL-2 and IFN-gamma mRNA, which is not increased by Hg, and a marked increase in IL-10 expression. Conversely, the key features of H-2-linked susceptibility to Hg- and Ag-induced AFA are up-regulation of IL-2, IFN-gamma and IL-4 mRNA expression, and down-regulation of IL-10 expression.
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PMID:Murine metal-induced systemic autoimmunity: baseline and stimulated cytokine mRNA expression in genetically susceptible and resistant strains. 1167 13

There is an emerging trend in the pharmaceutical industry to evaluate a variety of surrogate biomarkers in Phase I/II clinical studies with the intention of determining potential activity of drugs early in clinical development. A number of cytokines expressed in pathological conditions are currently being considered as potential surrogates of disease and/or drug activity. The quantitative measurement of such analytes (biomarkers) in biological fluids has traditionally been performed by bioassays, enzyme-linked immunosorbent assay (ELISA), ribonuclease protection assay (RPA) and polymerase chain reaction (PCR). Typically, these methods have been limited to the measurement of a single analyte, require large sample volume and are time and cost involved. The LabMAP (Luminex) system has been previously used to quantify cytokines in tissue culture supernatants and in animal serum. In the present study, the LabMAP technology was used for quantifying for the first time, pro-inflammatory cytokines such as, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), IL-6 and IL-8 levels in lipopolysaccharide (LPS)-stimulated human plasma samples. Both single-cytokine and two-cytokine (biplexed) panel formats were evaluated and the performance in the two formats was compared. A detailed validation procedure for these determinations is described along with a side-by-side comparison with ELISA results. Our results indicate that the LabMAP system can be used to measure cytokine levels in LPS-stimulated human plasma samples and that the levels obtained by this technique are comparable with ELISA results. It is therefore feasible to use this optimized technology to detect and quantify cytokines and other potential biomarkers in a complex milieu such as human plasma in support of clinical studies.
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PMID:Simultaneous quantification of proinflammatory cytokines in human plasma using the LabMAP assay. 1179 90

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

Exposure to chemicals in domestic and occupational settings may contribute to increases in asthma and allergy. Airway hypersensitivity (AHS) is T helper-2 (Th2) cell associated, whereas contact hypersensitivity (CHS) is T helper-1 (Th1) cell associated. The distinct cytokine profiles produced by these cells may provide a means of distinguishing respiratory sensitizers from contact sensitizers. In this study, female BALB/c mice were exposed twice on the flanks and three times on the ears using the airway sensitizer trimellitic anhydride (TMA) or the contact sensitizer dinitrochlorobenzene (DNCB). At various times following exposure, total mRNA was extracted from draining lymph node cells and cytokine mRNA profiles analyzed using a multiprobe ribonuclease protection assay (RPA). The Th2 cytokines IL4, IL10, and IL13 were significantly increased in response to TMA compared to DNCB, with optimal detection occurring 14 days following initial exposure. To determine its effect, dose was varied in flank exposures, ear exposures, or both simultaneously. When dose was varied during flank exposures only, TMA induced higher levels of Th2 cytokines than DNCB at all doses tested. DNCB did not induce Th1 cytokines at any dose tested. Variation of TMA dose during both exposures similarly induced Th2 cytokines. Dose only appeared to be a factor when TMA concentration was varied during the ear exposures alone. Thus, these studies suggest that quantitative differences in Th2 responses between TMA and DNCB may be demonstrated over a wide range of doses and these differences may be detected by RPA following dermal exposure to these sensitizers.
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PMID:Cytokine profiling for chemical sensitizers: application of the ribonuclease protection assay and effect of dose. 1249 39

Interleukin-15 (IL-15) is a proinflammatory cytokine with multifunctional effects outside the immune system. Previous studies have indicated that treatment of normal rats with IL-15 reduces white adipose tissue (WAT) mass, but it was unclear if these effects were direct or indirect. In the present study, the effects of IL-15 on WAT mass and lipid metabolism were studied in two genetic models of obesity: the leptin receptor-negative fa/fa Zucker rat and the leptin-deficient ob/ob mouse. Lean Zucker rats, lean (+/+), and obese mice (ob/ob) responded to IL-15 with reductions in WAT mass and lipoprotein lipase activity (LPL), with no decreases in food intake. In contrast, fa/fa Zucker rats did not respond to IL-15 administration by any of the above measures of fat mass or lipid metabolism. In addition, ribonuclease protection assays (RPAs) were used to demonstrate that all three subunits (gamma(c), beta and alpha) of the IL-15 receptor complex are expressed by rat and mouse WAT, suggesting that the effects of IL-15 on adipose tissue metabolism could be direct. Additionally, the fa/fa rats expressed 84% lower levels of the gamma(c) signaling receptor subunit than lean Zucker rats, suggesting this decrease may play a role in the lack of adipose tissue response to IL-15 in the fa/fa genotype and lending further support for a direct action of IL-15 on adipose tissue.
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PMID:Effects of interleukin-15 (IL-15) on adipose tissue mass in rodent obesity models: evidence for direct IL-15 action on adipose tissue. 1196 Jun 86

The effects of a 50 Hz extremely low frequency (ELF) sinusoidal magnetic field (MF) on the expression of genes relating to cytokine receptors were studied in HL60 cells. Transcription levels of tumor necrosis factor receptor (TNFR) p55 and p75, interleukin-6 receptor-alpha (IL-6Ralpha) and transforming growth factor-beta receptor 1 (TGFbetaR1) were quantified in cells exposed to an intensity of 0.1 or 0.8 mT for periods ranging from 30 min to 72 h. Cells treated with 10 nM of phorbol 12-myristate 13-acetate (PMA) for 8 h served as a positive control. Gene expression values were assessed by the ribonuclease protection assay (RPA) and normalized to those of the noninducible gene GAPDH. The results showed that MF exposure at 0.1 and 0.8 mT for 72 h increased TNFR p75 and IL-6Ralpha mRNA expression in HL60 cells. No significant change in gene expression levels of TNFR p55 and TGFbetaR1 was observed under any of the exposure conditions. In addition, we report here for the first time that IL-6Ralpha mRNA expression can be suppressed by PMA in HL60 cells.
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PMID:Gene expression of cytokine receptors in HL60 cells exposed to a 50 Hz magnetic field. 1211 54


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