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

Murine gammaherpesvirus 68 replicates in the alveolar epithelium and induces an inflammatory infiltrate in the lung, following intranasal challenge, and is cleared 10 and 13 days after infection by a T-cell-dependent mechanism. In order to understand the development of the immune response to this virus and how leukocyte trafficking to the lung is regulated, chemokine expression during MHV-68 infection was examined in lung tissue using an RNase protection assay. Expression of RANTES, eotaxin, MIP-1 alpha, MIP-1 beta, IP-10, and MCP-1 was upregulated by day 7 after infection. Chemokine concentrations in lung lavage fluid were also determined by ELISA. MCP-1, RANTES, MIP-1 alpha, eotaxin, and KC were upregulated during MHV-68 infection. Most of these chemokines have been reported to be chemoattractants for either activated T cells or monocytes, which are the major cellular components of the inflammatory infiltrate induced by the virus. Upregulated expression of the corresponding receptors for the chemokines, including CCR1, CCR2, CCR3, CCR5, and CXCR3, coincided with the development of the inflammatory infiltrate. The chemokine levels peaked at around day 7 after infection, coinciding with peak viral titers and slightly preceding maximal T cell infiltration. In vitro chemotaxis assays confirmed that lung lavage fluid from MHV-68-infected mice had chemotactic activity, which was partially blocked by antibodies to IP-10 and RANTES. These observations suggest that the chemokines detected play an important role in regulating leukocyte trafficking to the lungs during MHV-68 infection.
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PMID:Chemokine induction and leukocyte trafficking to the lungs during murine gammaherpesvirus 68 (MHV-68) infection. 1185 99

We systematically investigated the impact of the relative maturation levels of dendritic cells (DCs) on their cell surface phenotype, expression of cytokines and chemokines/chemokine receptors (by DNA array and RNase protection analyses), biological activities, and abilities to induce tumor immunity. Mature DCs expressed significantly heightened levels of their antigen-presenting machinery (e.g., CD54, CD80, CD86) and numerous cytokines and chemokines/chemokine receptors (i.e., Flt-3L, G-CSF, IL-1alpha and -1beta, IL-6, IL-12, CCL-2, -3, -4, -5, -17, and -22, MIP-2, and CCR7) and were significantly better at inducing effector T cell responses in vitro. Furthermore, mice vaccinated with tumor peptide-pulsed mature DCs better survived challenge with a weakly immunogenic tumor (8 of 8 survivors) than did mice vaccinated with less mature (3 of 8 survived) or immature (0 of 8 survivors) DCs. Nevertheless, intermediate-maturity DCs expressed substantial levels of Flt-3L, IGF-1, IL-1alpha and -1beta, IL-6, CCL-2, -3, -4, -9/10, -17, and -22, MIP-2, osteopontin, CCR-1, -2, -5, and -7, and CXCR-4. Taken together, our data clearly underscore the critical nature of employing DCs of full maturity for DC-based antitumor vaccination strategies.
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PMID:DNA array and biological characterization of the impact of the maturation status of mouse dendritic cells on their phenotype and antitumor vaccination efficacy. 1190 30

The intracerebral formation of inflammatory infiltrates is a complex process, which may be regulated by chemokines. This study defines the kinetics and cellular sources of T cell- and macrophage-attracting chemokines in murine Toxoplasma encephalitis (TE) by ribonuclease protection assay, reverse transcription-PCR, in situ hybridization, and immunohistochemistry. Whereas astrocytes were the major source of interferon (IFN)-gamma-inducible protein-10 (CRG-2/IP-10) and monocyte chemoattractant protein (MCP)-1, microglia expressed RANTES, monokine induced by IFN-gamma (MuMIG) and occasionally CRG-2/IP-10 RNA. Despite being ubiquitously activated, only astrocytes and microglia confined to inflammatory infiltrates expressed chemokine genes. Intracerebral leukocytes transcribed RANTES, MuMIG, and occasionally CRG-2/IP-10 and MCP-1. IFN-gamma-deficient mice failed to produce CRG-2/IP-10, MuMIG, RANTES and expressed macrophage inflammatory protein (MIP-1)alpha, MIP-1 beta, and MCP-1 mRNA at reduced levels, functionally resulting in a strongly reduced recruitment of leukocytes across the blood-brain barrier and prevented their further invasion of the brain parenchyma. Since T cells are the single source of IFN-gamma in TE, these findings indicate that T cells pave the way of leukocytes to parenchymatous parasites via IFN-gamma.
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PMID:Chemokines are differentially expressed by astrocytes, microglia and inflammatory leukocytes in Toxoplasma encephalitis and critically regulated by interferon-gamma. 1193 61

Chemokines are small chemoattractant cytokines which participate in the migration of immune cells into the CNS and contribute to the T cell-mediated pathogenesis of multiple sclerosis (MS). The expression of chemokines and their receptors in freshly isolated mononuclear cells from peripheral blood (PBMC) was studied in relation to MS subtype, disease duration and progression in a total of 57 patients with MS (22 relapsing remitting, RRMS; 21 secondary progressive, SPMS; 14 primary progressive, PPMS) and 17 healthy controls. The RNA expression of CCR5 in PBMC was analysed by reverse transcription polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. The PBMC levels of CCR5-ligands MIP-1 alpha/beta and RANTES, and chemokines MCP-1, IL-8, lymphotactin, IP-10 and I-309 were analysed by ribonuclease protection assay (RPA). Significantly increased intracellular CCR5 RNA expression intensity was detected in PPMS when compared with SPMS ( p=0.009), RRMS ( p=0.013), and controls ( p=0.023). However, the surface expression of CCR5 on CD4(+) cells from PBMC, analysed by flow cytometry, appeared to be similar in all MS subtypes and controls. The CCR5-ligands RANTES and MIP-1b were expressed constitutively in all patients and controls. Interleukin-8 was found in all MS subtypes and controls, but IP-10 was detected only in RRMS and SPMS, and lymphotactin occasionally in other subtypes but PPMS. MCP-1, MIP-1a or I-309 were not expressed in any of the groups studied. A correlation was found between the RNA levels of RANTES and CCR5 in PPMS ( r=0.735). Differential profile in the expression of CCR5 and chemokines between PPMS and other MS subtypes may contribute to differences in the pathogenesis of MS and thus can be of importance in the development of new treatments for MS.
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PMID:Differential intracellular expression of CCR5 and chemokines in multiple sclerosis subtypes. 1202 48

The inflammatory response initiated after spinal cord injury (SCI) is characterized by the accumulation of macrophages at the impact site. Monocyte chemoattractant protein-1 (MCP-1) is a strong candidate for mediating chemotaxis of monocytes to the injured nervous system. To help in defining the role of MCP-1 in inflammation after SCI, we evaluated the time course of macrophage accumulation for 2 weeks following a midthoracic spinal cord contusion injury in mice lacking CCR2, a principal receptor for MCP-1. Mice with a deletion of CCR2 resulted in significantly reduced Mac-1 immunoreactivity restricted to the lesion epicenter at 7 days postinjury. The regions devoid of Mac-1 immunoreactivity corresponded to areas of reduced myelin degradation at this time. By 14 days postinjury, however, there were no differences in Mac-1 staining between CCR2 (+/+) and CCR2 (-/-) mice. Analyses of mRNA levels by RNase protection assay (RPA) revealed increases in MCP-1 as well as MCP-3 and MIP-2 mRNA at 1 day postinjury compared with 7 day postinjury. There were no differences in chemokine expression between CCR2-deficient mice and wild-type littermate controls. The CCR2-deficient mice also exhibited reduced expression of mRNA for chemokine receptors CCR1 and CCR5. Together, these results indicate that chemokines acting through CCR2 contribute to the early recruitment of monocytes to the lesion epicenter following SCI.
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PMID:Monocyte recruitment and myelin removal are delayed following spinal cord injury in mice with CCR2 chemokine receptor deletion. 1211 30

The purpose of these studies was to examine the role of cytokines in the pathogenesis of cisplatin nephrotoxicity. Injection of mice with cisplatin (20 mg/kg) led to severe renal failure. The expression of cytokines, chemokines, and ICAM-1 in kidney was measured by ribonuclease protection assays and RT-PCR. We found significant upregulation of TNF-alpha, TGF-beta, RANTES, MIP-2, MCP-1, TCA3, IL-1beta, and ICAM-1 in kidneys from cisplatin-treated animals. In addition, serum, kidney, and urine levels of TNF-alpha measured by ELISA were increased by cisplatin. Inhibitors of TNF-alpha production (GM6001, pentoxifylline) and TNF-alpha Ab's reduced serum and kidney TNF-alpha protein levels and also blunted the cisplatin-induced increases in TNF-alpha, TGF-beta, RANTES, MIP-2, MCP-1, and IL-1beta, but not ICAM-1, mRNA. In addition, the TNF-alpha inhibitors also ameliorated cisplatin-induced renal dysfunction and reduced cisplatin-induced structural damage. Likewise, TNF-alpha-deficient mice were resistant to cisplatin nephrotoxicity. These results indicate cisplatin nephrotoxicity is characterized by activation of proinflammatory cytokines and chemokines. TNF-alpha appears to play a central role in the activation of this cytokine response and also in the pathogenesis of cisplatin renal injury.
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PMID:TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. 1223 3

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

Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that has been suggested to act as a cofactor in the progression of HIV disease. Exposure of human macrophages to HHV-6A or HHV-6B profoundly impaired their ability to produce interleukin 12 (IL-12) upon stimulation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). By contrast, the production of tumor necrosis factor-alpha (TNF-alpha); regulated on activation, normal T-cell expressed and secreted (RANTES); and macrophage inflammatory protein 1 beta (MIP-1 beta) was not negatively affected. To exclude the involvement of IL-12-suppressive cytokines, such as IL-10 and TNF-alpha, the viral stocks were fractionated by ultra-centrifugation. The bulk of the suppressive activity was recovered within the virion-rich pelleted fraction that was virtually devoid of such cytokines. IL-12 suppression was independent of viral replication, and the effect was not abrogated upon ultraviolet-light inactivation of the viral inoculum. The mechanism of HHV-6-mediated IL-12 suppression was investigated by RNase protection assays, which demonstrated unaltered levels of IL-12 p35 mRNA and only a modest reduction in p40 mRNA, which was insufficient to account for the near-complete loss of both extracellular and intracellular IL-12 protein. Moreover, both the IFN-gamma and the LPS signaling pathways were intact in HHV-6-treated cells. These data suggest that HHV-6 can dramatically affect the generation of effective cellular immune responses, providing a novel potential mechanism of HHV-6-mediated immunosuppression.
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PMID:Selective suppression of IL-12 production by human herpesvirus 6. 1282

Restraint stress (RS) applied to mice during acute infection with Theiler's virus causes corticosterone-induced immunosuppression. This effect was further investigated by measuring chemokine changes in the spleen and central nervous system (CNS) using an RNase Protection Assay. mRNAs for lymphotactin (Ltn), interferon-induced protein-10 (IP-10), MIP-1 beta, monocyte chemoattractant protein-1 (MCP-1) and TCA-3 were detected in the spleen at day 2 pi, but not in the brain of CBA mice infected with Theiler's virus. Ltn, IP-10 and RANTES were elevated in both the spleen and the brain at day 7 pi, and were significantly decreased by RS in the brain. RS also resulted in decreased inflammation within the CNS.
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PMID:Alterations in chemokine expression following Theiler's virus infection and restraint stress. 1514 9

Antigen-stimulated naive CD4 T cells may differentiate into effector T cells such as Th1 and Th2 cells, or may remain as proliferating but uncommitted, primed, precursor cells (Thpp cells) that can subsequently differentiate into Th1 or Th2 cells in appropriate cytokine environments. To examine potential Thpp effector functions, we compared the genes expressed by mouse Thpp, naive, Th1 and Th2 cells, using Affymetrix GeneChip and RNase Protection assays. Similar to naive CD4 T cells, Thpp cells expressed IL-2 but not the cytokines characteristic of differentiated Th1 or Th2 cells, such as IFN-gamma, IL-4, or IL-5. However, Thpp, Th1 and Th2 cells, but not naive cells, expressed several CC chemokines including CCL1/TCA3, CCL5/RANTES, CCL3/MIP-1 alpha, CCL4/MIP-1 beta, and CCL9/MIP-1 gamma. Secretion of the corresponding proteins was confirmed by ELISA and Elispot. Consistent with this chemokine expression, supernatants of activated Thpp, Th1 and Th2 cells but not naive CD4T cells induced pertussis toxin-sensitive chemotaxis of B and T cells. Supernatants of Thpp cells did not bias differentiation of naive CD4 T cells towards either Th1 or Th2 cells. The secretion of several chemokines, but few cytokines, by primed uncommitted Thpp cells suggests that their activation during an immune response may recruit effector cells without directly polarizing effector functions.
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PMID:Synthesis of several chemokines but few cytokines by primed uncommitted precursor CD4 T cells suggests that these cells recruit other immune cells without exerting direct effector functions. 1516 31


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