Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNase protection analysis using p75, trk A, and trk B RNA probes was used to examine mRNA expression in rat tissues, with particular emphasis on the immune system. Every tissue examined, with the exception of postnatal day 0 spleen, expressed p75 mRNA. Trk A mRNA was observed in tissues previously reported to be negative for the trk A receptor, such as kidney, thymus, lymph node, muscle, and lung. Neuronal tissues expressed only the long form of trk A, whereas nonneuronal tissues expressed both trk A forms. Trk B mRNA was expressed by the same tissues as trk A, plus heart and spleen. Neuronal tissues expressed full-length and truncated trk B, whereas nonneuronal tissues only expressed truncated trk B. During development of the thymus p75 mRNA levels increased and trk A mRNA levels decreased. Similarly, for the spleen, p75 mRNA levels increased and those of trk B decreased during development. The expression of p75, trk A and trk B was localized primarily to the stroma of the thymus and spleen, but there was some expression by the splenocytes and thymocytes. The widespread expression of neurotrophin receptors in areas not known to be targets for neurotrophins suggests broader functions for neurotrophins outside of the nervous system.
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PMID:Widespread neurotrophin receptor expression in the immune system and other nonneuronal rat tissues. 789 Nov 6

In order to examine the regulation of cytokine receptor gene expression an RNase protection assay (RPA) was developed that allows the simultaneous and semiquantitative measurement of mRNAs encoding for the IL-1 p60 and p80, TNF p55 and p75, IFN-gamma, and IL-6 receptors. Titration experiments revealed that this method was very sensitive allowing the detection of the target cytokine receptor mRNAs down to at least 0.01 microgram of spleen poly(A)+ RNA. The cytokine receptor RPA was used to examine the expression of the receptor genes in various organs from normal mice and mice that had been injected with LPS. In normal mice expression of the IL-1R p80, TNFR p55 and p75, IFN-gamma, and IL-6R but not the IL-1R p60 transcripts was readily detectable in spleen, liver, kidney, and brain. Following LPS treatment, there was an induction of the IL-1R p60 mRNA in all organs and an up-regulation of the IL-1R p80, TNFR p55 and p75, IFN-gamma, and IL-6 receptor mRNAs particularly in spleen, liver, and kidney. Interorgan differences were observed in the regulation of these receptor mRNAs, indicating an organ-specific response to the LPS challenge. Our findings indicate the cytokine receptor RPA is a powerful and versatile tool for the simultaneous analysis of multiple cytokine receptor mRNAs in tissue samples. This technique will prove valuable in further evaluating the coordinated regulation of the expression of these genes, which are pivotal in the biology of cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Simultaneous analysis of multiple cytokine receptor mRNAs by RNase protection assay in LPS-induced endotoxemia. 806 Nov 11

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.
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PMID:Barrier disruption increases gene expression of cytokines and the 55 kD TNF receptor in murine skin. 920 92

The chance of life-threatening complications occurring late after brain irradiation limits the efficacy of this form of cancer therapy. The molecular and cellular events that trigger radiation-induced brain damage are still unknown, but since they have the potential to serve as valuable targets for therapeutic intervention they are worth delineating. In this murine study, the effect of irradiation on the expression of molecules which are known to contribute to brain damage in other model systems was examined. Expression of genes encoding cytokines (TNF-alpha/beta, IL-1 alpha/beta, IL-2, IL-3, IL-4, IL-5, IL-6 and IFN-gamma), cytokine receptors (TNF-Rp55 and p75, IL-1R- p60 and p80, IFN-gamma R, and IL-6R), the cell adhesion molecule (ICAM-1), inducible nitric oxide synthetase (iNOS), anti-chymotrypsin (EB22/5.3), and the gliotic marker (GFAP) was evaluated over a 6-month period using a sensitive RNase protection assay (RPA). We had previously demonstrated that within 24 h of brain irradiation there is an acute transitory molecular response involving TNF-alpha, IL-1, ICAM-1, EB22/5.3 and GFAP. This study shows re-elevation of TNF-alpha, EB22/5.3 and GFAP mRNA levels at 2-3 months, but only TNF-alpha mRNA was overexpressed at 6 months. These time points are when neurological abnormalities are seen after higher doses. The data suggest that TNF-alpha may be involved in late brain responses to irradiation and could contribute to clinical symptoms.
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PMID:Delayed molecular responses to brain irradiation. 924 93

Tumor necrosis factor (TNF) receptor (TNFR)-associated factors 1 and 2 (TRAF1 and TRAF2) and inhibitor of apoptosis proteins cIAP1 (MIHB) and cIAP2 (MIHC) were recently identified as proteins that associate with the TNF-alpha receptors TNFRI (p55) and TNFRII (p75) and inhibit TNF-alpha-induced programmed cell death or apoptosis. In the original reports, TRAF1 expression, unlike the ubiquitous TRAF2, was restricted to specific tissues in the lung, spleen, and testis. TNF-alpha is increased in the lung in many forms of pulmonary disease. In the current study, Western analysis, immunohistochemistry, and ribonuclease protection assays were used to determine whether TNF-alpha regulates the expression of these TNFR-associated proteins in lung cells. We demonstrate for the first time TNF-alpha dose-dependent induction of TRAF1 protein and messenger RNA (mRNA) in human H441 and A549 pulmonary adenocarcinoma cell lines, as well as in lung cells of C57BL/6J mice after intratracheal administration of TNF-alpha. In contrast to the epithelial cells, TRAF1 was not induced by TNF-alpha in U937 cells, a human monocytic cell line, suggesting cell type-specific regulation. Similarly, cIAP2 mRNA was induced by TNF-alpha in both H441 and A549 pulmonary epithelial cells but not in U937 cells. TNF-alpha is a primary mediator of acute pulmonary inflammation and contributes to the pathophysiology of chronic lung diseases such as bronchopulmonary dysplasia (BPD), a fibrotic disease of prematurely born infants. Immunohistochemical staining of human neonatal lung tissue demonstrated increased TRAF1 in lungs of infants dying of pneumonia or BPD in comparison with those dying of congenital malformation. These studies support the hypothesis that the TRAF1 and cIAP2 genes are highly regulated in pulmonary cells and may play a role in human lung disease.
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PMID:Tumor necrosis factor-alpha-induced lung cell expression of antiapoptotic genes TRAF1 and cIAP2. 1065 35

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

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-kappaB binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-kappaB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-gamma, RANTES, TNF-alpha, TNFR p75, IL-1beta in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.
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PMID:Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible? 1254 79

Previous studies suggest that tumor necrosis factor alpha (TNF-alpha) and the TNFRI (p55) and TNFRRII (p75) receptors mediate the pulmonary fibrotic response to silica. In order to further define the role of the TNFRI (p55) receptor in induction of profibrotic chemokines by low-dose silica/crystalline silica (50 micro g/50 micro l/mouse) or control diluent saline was instilled into the trachea of TNFRI gene ablated ((-/-)) and C57BL/6 (WT) control mice. Lung tissue was harvested and bronchoalveolar lavage (BAL) performed 24 h and 28 days following silica administration. Selected profibrotic chemokine mRNAs were quantified by ribonuclease protection assay, normalized to ribosomal protein L32 mRNA content and expressed relative to saline control treated lungs. Induction of MIP-1beta, MIP-1alpha, MIP-2, IP-10, and MCP-1 mRNAs was attenuated in the TNFRI(-/-) mice, in comparison to WT mice, particularly at 28 days after exposure. ELISA assays for MIP-1alpha and MIP-2 in homogenized lung tissue similarly demonstrated marked induction of both chemokines 24 h after silica treatment, which was persistent at 28 days in WT but not in TNFRI(-/-) mice. The percentage of BAL cells that was neutrophils was comparably increased in WT and RI(-/-) lungs at 24 h (49 +/- 12% vs. 46 +/- 10%) and 28 days (6.2 +/- 1.5% vs. 4.5 +/- 1%). The increase in total lavagable cells and BAL protein was also independent of strain. Histology revealed mild alveolitis without granuloma formation in both strains, slightly decreased in TNFRI(-/-). This study demonstrates an increase in pro-fibrotic chemokines in response to a single intratracheal exposure to crystalline silica that was sustained at 28 days after treatment in WT but not in TNFRI(-/-) mice. Silica dependent recruitment of neutrophils to the alveolar space and alveolar protein leak were, however, not altered by the absence of the TNF receptor.
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PMID:Induction of chemokines by low-dose intratracheal silica is reduced in TNFR I (p55) null mice. 1260 44

Recent studies from our laboratory demonstrate that TNF-alpha signaling contributes to the regulation of chondrocyte apoptosis and a lack of TNF-alpha signaling leads to a persistence of cartilaginous callus and delayed resorption of mineralized cartilage. This study examines how delays in the endochondral repair process affect the expression of specific mediators of proteolytic cartilage turnover and vascularization. Simple closed fractures were produced in wild type and TNF-alpha receptor (p55-/-/p75-/-)-deficient mice. Using ribonuclease protection assay (RPA) and microarray analysis, the expression of multiple mRNAs for various angiogenic factors and the metalloproteinase gene family were measured in fracture calluses. The direct actions of TNFalpha on the expression of specific angiogenic factors and metalloproteinases (MMPs) was examined in both cultured callus cells and articular chondrocytes to compare the effects of TNF-alpha in growth cartilage versus articular cartilage. MMPs 2, 9, 13, and 14 were quantitatively the most prevalent metalloproteases and all showed peaks in expression during the chondrogenic period. In the absence of TNF-alpha signaling, the expression of all of these mRNAs was reduced. The angiopoietin families of vascular regulators and their receptors were expressed at much higher levels than the VEGFs and their receptors and while the angiopoietins showed diminished or delayed expression in the absence of TNF-alpha signaling, VEGF and its receptors remained unaltered. The expression of vascular endothelial growth inhibitor (VEGI or TNFSF15) showed a near absence in its expression in the TNF-alpha receptor-deficient mice. In vitro assessment of cultured fracture callus cells in comparison to primary articular chondrocytes showed that TNF-alpha treatment specifically induced the expression of MMP9, MMP14, VEGI, and Angiopoietin 2. These results suggest that TNF-alpha signaling in chondrocytes controls vascularization of cartilage through the regulation of angiopoietin and VEGI factors which play counterbalancing roles in the induction of growth arrest, or apoptosis in endothelial cells. Furthermore, TNF-alpha appears to regulate, in part, the expression of two key proteolytic enzymes, MMP 9 and MMP14 that are known to be crucial to the progression of vascularization and turnover of mineralized cartilage. Thus, TNF-alpha signaling in healing fractures appears to coordinate the expression of specific regulators of endothelial cell survival and metalloproteolytic enzymes and is essential in the transition and progression of the endochondral phase of fracture repair.
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PMID:Tumor necrosis factor alpha (TNF-alpha) coordinately regulates the expression of specific matrix metalloproteinases (MMPS) and angiogenic factors during fracture healing. 1578 Sep 56