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:3.1.26.9 (ribonuclease)
6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemokines play a major role in the recruitment of inflammatory cells during acute lung injury. Adult and newborn C57BL/6 mice were exposed to > 95% oxygen for up to 72 hours and 7 days, respectively. Chemokine mRNA abundance was evaluated in whole lung RNA by ribonuclease protection assay and in tissue sections by in situ hybridization. Monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-2, and interferon gamma-induced protein (IP)-10 mRNAs were present in whole newborn lung by 4 days of hyperoxia and were markedly elevated by 7 days. Levels of mRNA for MCP-1, MIP-1 alpha, and MIP-2 were elevated to a lesser extent by 72 hours of hyperoxia in adults. MCP-1 mRNA abundance was moderately elevated in scattered areas of perivascular tissue, peribronchiolar tissue, and the alveolar interstitium in 4-day hyperoxic newborns and markedly upregulated diffusely throughout the peripheral airspaces in 7-day hyperoxic newborns. MCP-1 mRNA abundance was limited to scattered perivascular areas and airspaces in 72-hour hyperoxic adults. These differences in the intensity, timing, and distribution of chemokine mRNA abundance between adult and newborn mice may help to explain the marked differences in their susceptibility to oxygen injury.
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PMID:Chemokine mRNA alterations in newborn and adult mouse lung during acute hyperoxia. 977 77

Chemotactic cytokines (chemokines) play an important role in the recruitment of lymphocytes to tissue by regulating cellular adhesion and transendothelial migration. This study examined the expression and function of CXC (human monokine induced by gamma-interferon [HuMig], interleukin-8 [IL-8], and interferon-inducible protein-10 [IP-10]) and CC (macrophage inflammatory protein-1alpha [MIP-1alpha], MIP-1beta, regulated upon activation normal T lymphocyte expressed and secreted (RANTES), and macrophage chemoattractant protein-1 [MCP-1]) chemokines and their respective receptors on lymphocytes infiltrating human liver tumors. Chemokine and chemokine receptor expression was assessed by immunohistochemistry, flow cytometry, in situ hybridization and ribonuclease (RNAse) protection assays and function by in vitro chemotaxis of tumor-derived lymphocytes to purified chemokines and to HepG2 tumor cell culture supernatants. Tumor-derived lymphocytes showed strong chemotactic responses to both CC and CXC chemokines in vitro and expressed high levels of CXCR3 (HuMig and IP-10 receptor) and CCR5 (RANTES, MIP-1alpha, and MIP-1beta receptor). Expansion of tumor-derived lymphocytes in recombinant IL-2 increased expression of CXCR3. The corresponding chemokines were detected on vascular endothelium (HuMig, IL-8, MIP-1alpha, and MIP-1beta) and sinusoidal endothelium (HuMig, MIP-1alpha, MIP-1beta) in hepatocellular carcinoma. In vitro, HepG2 cells secreted functional chemotactic factors for tumor-derived lymphocytes that could be inhibited using anti-CCR5 or anti-CXCR3 monoclonal antibodies (MoAbs). Thus, lymphocytes infiltrating human liver tumors express receptors for and respond to both CXC and CC chemokines. The relevant chemokine ligands are expressed in hepatocellular carcinoma (HCC), particularly HuMig, which was strongly expressed by tumor endothelium, suggesting that they play a role in lymphocyte recruitment to these tumors in vivo. The ability of HepG2 cells to secrete lymphocyte chemotactic factors in vitro suggests that the tumor contributes to lymphocyte recruitment in vivo.
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PMID:Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma. 1038 45

Ozone (O(3)) and nitrogen dioxide (NO(2)) are highly reactive and toxic oxidant pollutants. The objective of this study is to compare chemokine, cytokine, and antioxidant changes elicited by acute exposures of O(3) and NO(2) in a genetically sensitive mouse. Eight-week-old C57Bl/6J mice were exposed to 1 or 2.5 ppm ozone or 15 or 30 ppm NO(2) for 4 or 24 h. Changes in mRNA abundance in lung were assayed by slot blot and ribonuclease protection assay (RPA). Messages encoding metallothionein (Mt), heme oxygenase I (HO-I), and inducible nitric oxide synthase (iNOS) demonstrated increased message abundance after 4 and 24 h of exposure to either O(3) or NO(2). Furthermore, increases in message abundance were of a similar magnitude for O(3) and NO(2). Messages encoding eotaxin, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 were elevated after 4 and 24 h of exposure to 1 ppm ozone. Interleukin-6 was elevated after 4 h of exposure to ozone. After 4 h of 2.5 ppm ozone exposure, increased mRNAs of eotaxin, MIP-1alpha, MIP-2, Mt, HO-I, and iNOS were elevated to a higher magnitude than were detected after 1 ppm ozone. Monocyte chemoattractant protein (MCP-1) was elevated following 15 ppm NO(2) exposure. After 4 h of 30 ppm NO(2) exposure, messages encoding eotaxin, MIP-1alpha, MIP-2, and MCP-1 were elevated to levels similar to those detected after ozone exposure. Our results demonstrate a similar antioxidant and chemokine response during both O(3) and NO(2) exposure. Induction of these messages is associated with the duration and concentration of exposure. These studies suggest that these gases exert toxic action through a similar mechanism.
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PMID:Antioxidant and inflammatory response after acute nitrogen dioxide and ozone exposures in C57Bl/6 mice. 1071 24

The ribonuclease protection assay (RPA) represents a sensitive method to detect and quantify RNA levels. It can be adapted to allow the simultaneous analysis of more than 10 different mRNAs. The multiprobe RPA kit mCK-5 from PharMingen was used to analyze the expression of chemokines in CCR5 chemokine receptor knockout mice. Upon careful analysis it was found that the mCK-5 kit is defective and can lead to false results for the chemokines IP-10 and MCP-1. The problem is caused by a long-known sequence polymorphism within the 3'-untranslated region of the murine IP-10 gene. This polymorphism leads to a protected IP-10 fragment approximately 20 nucleotides shorter than expected, yielding a length similar to the protected MCP-1 fragment from the mCK-5 kit. Since the identification of specific transcripts with this kit is based exclusively on the size of the various protected fragments, false-negative results for IP-10 together with false-positive results for MCP-1 can be obtained. Interestingly, the polymorphism was found not only in 129/CD-1 mice, but also in MRL and SJL/J mice. To facilitate troubleshooting in the future, all templates from the mCK-5 set were isolated and sequenced.
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PMID:The mCK-5 multiprobe RNase protection assay kit can yield erroneous results for the murine chemokines IP-10 and MCP-1. 1106 40

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

Bone infection or osteomyelitis is characterized by uncontrolled inflammation and destructive bone loss although little is known about immunopathogenesis of infection. We investigated control of chemokine secretion from osteoblasts infected with either Mycobacterium tuberculosis, which normally elicits a granulomatous host response, or Staphylococcus aureus, which drives a host response dominated by neutrophil influx. We show that M. tuberculosis infection of cultured and primary osteoblasts induces extensive secretion of the chemokines interleukin (IL)-8, inducible protein (IP) 10, RANTES, and monocyte chemoattractant protein (MCP) 1 within 72 h (1630 +/- 280 pg/ml per 4 x 10(5) cells, 74,130 +/- 8480 pg/ml per 4 x 10(5) cells, 18,330 +/- 3040 pg/ml per 4 x 10(5) cells, and 138,670 +/- 13,340 pg/ml per 4 x 10(5) cells, respectively, for MG-63 osteoblasts). S. aureus infection also results in secretion of these chemokines but secretion is delayed and of lesser magnitude (210 +/- 10 pg/ml per 4 x 10(5) cells, 11,570 +/- 1240 pg/ml per 4 x 10(5) cells, 930 +/- 34 pg/ml per 4 x 10(5) cells, and 13,770 +/- 720 pg/ml per 4 x 10(5) cells for IL-8, IP-10, RANTES, and MCP-1, respectively). The minimal up-regulation of secretion of the neutrophil attractant IL-8 in staphylococcal infection is both striking and unexpected. In both infections, chemokine secretion was dependent on the presence of live organisms. Differences in kinetics and magnitude of chemokine secretion are associated with distinct patterns of mRNA expression, as assessed by ribonuclease protection assay (RPA) and reverse-transcription polymerase chain reaction (RT-PCR). In addition, nuclear localization of the transcription factor activator protein (AP) 1 in M. tuberculosis-infected osteoblasts also is distinct as compared with S. aureus-infected cells. In summary, this study shows that osteoblasts have an important pathogen-specific role in control of chemokine gene expression and secretion during the human immune response to osteomyelitis.
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PMID:Differential regulation of chemokine secretion in tuberculous and staphylococcal osteomyelitis. 1221 39

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

We previously demonstrated doxorubicin-induced urokinase expression in human H69 SCLC cells by the microarray technique using Human Cancer CHIP version 2 (Takara Shuzo, Kyoto, Japan), in which 425 human cancer-related genes were spotted on glass plates (Kiguchi et al., Int J Cancer 2001;93:792-7). Microarray analysis also revealed significant induction of IL-8, a member of the CXC chemokines. We have, therefore, extended the observation by testing the effects of doxorubicin on expression of the chemokine family and provide here definitive evidence that doxorubicin induces IL-8 and MCP-1, one of the CC chemokines, at least in 2 human SCLC cells, H69 and SBC-1. IL-8 antigen levels, measured by ELISA, were markedly increased in both H69 and SBC-1 conditioned media after doxorubicin treatment, in parallel with mRNA levels; and this was dependent on the dose of doxorubicin. The ribonuclease protection assay, using a multiprobe template set for human chemokines, revealed induction of not only IL-8 but also MCP-1 in doxorubicin-treated H69 cells. MCP-1 antigen levels increased approximately 100-fold in doxorubicin-treated H69 cells. RT-PCR using specific primers for MCP-1 suggested that doxorubicin also induced MCP-1 expression in SBC-1 and SBC-3 SCLC cells. Futhermore, CAT analysis using IL-8 promoter implicated the PEA3 transcriptional factor, whose binding site was located immediately upstream of the AP-1 and NF-kappaB binding sites. Thus, it is suggested that doxorubicin induces IL-8 and MCP-1 chemokines in human SCLC cells by activating gene expression, in which at least PEA3 is involved. IL-8 and MCP-1 are major chemoattractants for neutrophils and monocytes/macrophages, respectively; therefore, extensive induction of IL-8 and MCP-1 may provoke the interaction between inflammatory/immune cells and tumor cells under doxorubicin stimulation and influence many aspects of tumor cell biology.
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PMID:Induction of IL-8 and monoclyte chemoattractant protein-1 by doxorubicin in human small cell lung carcinoma cells. 1247 21

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


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