Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calprotectin, a heterodimer of MRP8 and MRP14 with antimicrobial properties, is found in the cytosol of neutrophils, monocytes, and human gingival keratinocytes. During inflammation of the oral mucosa, the expression of immunoreactive calprotectin appears upregulated. Given the possible cell sources, we sought to learn if epithelial cells upregulate calprotectin in response to proinflammmatory agents. First, human gingival keratinocytes were maintained in primary culture until senescence. At each passage, cells were harvested and analyzed for quantitative expression of MRP8 and MRP14 subunit mRNA by RNase protection assays and calprotectin complex by enzyme-linked immunosorbent assay. Calprotectin expression was constitutive in the primary gingival keratinocytes, but calprotectin-specific mRNA and protein tended to increase as the cells neared senescence. To test whether calprotectin expression was inducible, immortalized gingival keratinocyte cultures were treated for 2 to 4 h with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta). As a positive control for inducible expression, immortalized keratinocytes were incubated with phorbol myristate acetate (PMA) (50 ng/ml) for 24 h. Incubation with PMA stimulated increased expression of MRP8 and MRP14 mRNA within 2 h, peaking within 5 h. MRP8- and MRP14-specific mRNA expression by immortalized keratinocytes appeared to be unaffected by LPS or IL-1 beta. In contrast, LPS, IL-1 beta, and PMA each upregulated IL-8. These data show that calprotectin mRNA is expressed constitutively in cultured keratinocytes, while expression by immortalized cells appears to be independent of the exogenous proinflammatory agents LPS and IL-1 beta.
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PMID:Calprotectin expression by gingival epithelial cells. 1129 47

Pseudomonas aeruginosa is an opportunistic pathogen which causes sight-threatening corneal infections in humans. The purpose of this study was to evaluate various immunization routes that may provide protection against Pseudomonas keratitis and to define the molecular mechanisms involved in the protection. Sprague-Dawley rats (10 to 12 weeks old) were immunized using paraformaldehyde-killed P. aeruginosa (strain 6206) via oral, nasal, and intra-Peyer's patch (IPP) routes followed by an ocular topical booster dose. Scratched corneas were challenged with an infective dose of P. aeruginosa. Following clinical examination, eyes were enucleated for histology, polymorphonuclear leukocyte (PMN) quantitation, bacterial count, enzyme-linked immunosorbent assay, and RNase protection assay. PMN infiltration was higher early (4 h) during the infection in immunized rats than in nonimmunized rats. Later during the infection, the number of PMNs diminished in immunized rats while in nonimmunized animals the number of PMNs continued to increase. Bacteria were cleared much faster from immunized groups than from the nonimmunized group, and the nasally immunized group had the most efficacious response among the immunized groups. Nasal and IPP immunization groups had increased cytokine expression of interleukin-2 (IL-2) and IL-5 and differed from each other for IL-6. All three immunized groups had significantly reduced IL-1 beta levels when compared with the nonimmunized rats and a significantly altered profile for CINC-1 expression. This study has shown that the route of immunization modulates the inflammatory response to ocular P. aeruginosa infection, thus affecting the severity of keratitis and adverse pathology, with nasal immunization being the most effective.
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PMID:Effector mechanisms of protection against Pseudomonas aeruginosa keratitis in immunized rats. 1129 52

Pseudomonas aeruginosa infection, one of the major complications of burn wounds, may lead to sepsis and death. Using the Multi-Probe Template/RNase protection assay, we have compared the expression of different cytokine genes within the skin and livers of thermally injured mice infected with P. aeruginosa PAO1. Thermal injury alone enhanced or up-regulated certain cytokines, including macrophage colony-stimulating factor (M-CSF), interleukin 1 (IL-1)RI, IL-1 beta, macrophage inflammatory protein (MIP)-1 beta and MIP-2; while PAO1 challenge alone up-regulated tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) expression. The combination of thermal injury plus PAO1 infection enhanced the expression of several pro-inflammatory and haematopoietic cytokines [stem cell factor (SCF), leukocyte inhibitory factor (LIF), IL-6 and TNF-alpha]; induced the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF by 5 h and the expression of additional cytokines, including TGF-beta, TNF-beta, lymphotoxin beta (LT-beta), interferon gamma (IFN-gamma), and IFN-beta by 40 h post-burn/infection. While the most intense cytokine expression occurred in the skin, the majority of cytokines tested were also expressed in the liver by 40 h post-burn/infection. These results suggest that in P. aeruginosa infection of burn wounds: (1) up-regulation of the expression of different cytokines, locally and within the livers of burned mice, is an indication of P. aeruginosa -induced sepsis; and (2) IL-6 and G-CSF play an important role in the host response mechanism.
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PMID:The effects of infection of thermal injury by Pseudomonas aeruginosa PAO1 on the murine cytokine response. 1179 26

The purpose of this study was to elucidate the expression of pro- and anti-inflammatory cytokines in mouse corneas infected with Pseudomonas aeruginosa. Three bacterial strains (invasive, cytotoxic, or CLARE [contact lens-induced acute red eye]) which have recently been shown to produce distinct patterns of corneal disease in the mouse were used. The left mouse (BALB/c) corneas were scarified and infected with 2 x 10(6) CFU of one of the three P. aeruginosa strains, while right eyes served as controls. Animals were examined at 1, 4, 8, 16, and 24 h with a slit lamp biomicroscope to grade the severity of infection. Following examination, eyes were collected and processed for histopathology, multiprobe RNase protection assay for cytokine mRNA, enzyme-linked immunosorbent assay to quantitate cytokine proteins, and myeloperoxidase activity to quantitate polymorphonuclear leukocytes. The kinetics of appearance and magnitude of expression of key cytokines varied significantly in the three different phenotypes of P. aeruginosa infection. The predominant cytokines expressed in response to all three phenotypes were interleukin-1 beta (IL-1 beta), IL-1Ra, and IL-6. In response to the invasive strain, which induced severe corneal inflammation, significantly lower ratios of IL-1Ra to IL-1 beta were present at all time points, whereas corneas challenged with the CLARE strain, which induced very mild inflammation, showed a high ratio of IL-1Ra to IL-1 beta. The outcome of infection in bacterial keratitis correlated with the relative induction of these pro- and anti-inflammatory cytokines, and exogenous administration of recombinant rIL-1Ra (rIL-1Ra) was able to reduce the disease severity significantly. These findings point to the therapeutic potential of rIL-1Ra protein in possible treatment strategies for bacterial keratitis.
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PMID:Balance of pro- and anti-inflammatory cytokines correlates with outcome of acute experimental Pseudomonas aeruginosa keratitis. 1189 86

In light of the important role of cytokines in the pathogenesis of bacterial infections, we analyzed the cytokine production induced by different Staphylococcus aureus (S. aureus), S. epidermidis and S. saprophyticus strains in human mononuclear cells (MNCs). MNCs secreted high amounts of interleukin-1beta (IL-1beta) and IL-6 proteins in responses to stimulation with all three species of Staphylococci. Interestingly, a large majority of the S. aureus strains induced significantly higher IL-12 and interferon (IFN) titers than did the S. epidermidis and S. saprophyticus strains. The RNase protection assay revealed high increases in IL-1alpha, IL-1 beta, IL-1 receptor antagonist, IL-6 and IL-12 p40 transcript levels in MNCs stimulated with Staphylococci. All of the tested Staphylococcal strains proved highly efficient in mediating the induction of these genes. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis indicated considerable increases in IFNA transcript levels in MNCs stimulated with S. aureus strains, while only a very weak expression was stimulated by S. epidermidis and S. saprophyticus. These results confirm that heat-killed Staphylococci exert strong immunomodulatory effects, and suggest that the contribution of T-helper 1 (Th(1)) cells to the immune response may be much extensive in infections caused by S. aureus strains, due to their high IL-12p70 and IFN-alpha-inducing activities.
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PMID:Induction of cytokine production by different Staphylococcal strains. 1229 15

Tissue factor (TF) initiates the extrinsic coagulation cascade on the surface of macrophages and endothelial cells. In septic patients, the extrinsic coagulation cascade is activated. When septic patients are febrile, mortality is decreased. The purpose of this study was to investigate the role of elevated temperatures on TF expression by endothelial cells during a sepsis-like challenge. Human endothelial vein cells (HUVECs) were incubated with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta) for 0, 2, 4, 6, or 8 h. At the 0-h time point, some HUVECs were heat shocked at 43 degrees C for 2 h and then recovered at 37 degrees C for 0, 2, 4, or 6 h. Heat-shocked and non-heat-shocked LPS-stimulated HUVECs were analyzed for TF-specific mRNA expression by ribonuclease protection assay (RPA), surface TF expression by flow cytometry, and TF activity by a two-stage clotting assay. Heat shocked LPS-stimulated HUVECs expressed significantly reduced TF-specific mRNA, TF surface protein levels, and TF surface activity when compared with non-heat-shocked, LPS-stimulated HUVECs (p < 0.0125, p < 0.0125, and p < 0.0001, respectively; repeated measures analysis of variance, ANOVA). If heat shock models elevated core temperature, these results suggest that fever may protect the host during sepsis by reducing TF activity on the surface of endothelial cells.
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PMID:The modulation of tissue factor by endothelial cells during heat shock. 1253 87

The temporal course of cerebral cytokine gene expression was investigated in the ME7/CV murine scrapie model to determine any association with neuropathological events. Analysis by RNase protection assay (RPA) demonstrated no transcripts for ILs 2, 3, 4, 5, 6, 7, 10, 12p40 and 13, granulocyte macrophage colony-stimulating factor, IFN-gamma or lymphotoxin-alpha at any time during the course of this disease. Transcripts for transforming growth factor-beta 1 were constitutively expressed in both control and scrapie-infected brain and were elevated at terminal disease. RPA and quantitative real-time RT-PCR detected low levels of transcripts for IL-1 alpha, IL-1 beta and TNF alpha in scrapie-infected brain but only IL-1 beta was elevated consistently in all mice studied. Although glial cell activation within the hippocampus was evident from 100 days post-infection (p.i.), elevated IL-1 beta transcripts (and immunoreactivity) were evident from 180 days p.i., around the time of hippocampal pyramidal neuron loss, and increased steadily thereafter to reach a 3.5-fold increase at terminal disease. Even at their maximum, levels of these transcripts were disproportionately low relative to the degree of glial cell activation. It is concluded that cytokine gene expression in the ME7 scrapie-infected mouse brain, relative to the degree of reactive gliosis, is highly restricted, temporally late and disproportionately low.
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PMID:Inducible cytokine gene expression in the brain in the ME7/CV mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease. 1291 82

Excessive proinflammatory cytokine and NO production by activated microglia play a role in neurodegenerative disorders. In this study, we found that a new compound KL-1037 suppressed LPS-induced NO release/inducible nitric oxide synthase expression in BV2 mouse microglial cells. In addition, KL-1037 prominently diminished LPS-induced production of pro-inflammatory cytokines such as TNF-alpha, IL-1 beta and IL-6, while it increased anti-inflammatory IL-10 and TGF-beta 1 production. By RNase protection assay and RT-PCR, we showed that KL-1037 regulated iNOS and cytokines at transcriptional or post-transcriptional level. Further analysis of molecular mechanisms revealed that KL-1037 prominently increased intracellular cAMP levels and potentiated LPS-induced pCREB expression. However, LPS-induced MAP kinase or NF-kappa B activities were slightly or little changed by KL-1037. Treatment with cAMP antagonist or IL-10 neutralizing antibody completely reversed upregulation of IL-10 and partially repression of TNF-alpha or NO induced by KL-1037. These data suggest that microglial inactivation by KL-1037 is at least in part due to activation of PKA pathway and/or upregulation of IL-10. Thus, repressing proinflammatory cytokines and iNOS gene expression in activated microglia by KL-1037 may provide potential therapeutic strategies for various neurodegenerative diseases including ischemic cerebral disease.
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PMID:A new anti-inflammatory agent KL-1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia. 1522 3


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