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

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the role of the cytochrome P-450 system in NO synthesis, cytochrome P-450IIIA, IIE and IA activities were specifically inhibited by cimetidine (IIIA), clotrimazole (IIIA), benzoflavone (IA) and disulfiram (IIE) in a model of cultured rat hepatocytes. Cytokine-induced NO synthesis was significantly decreased in the presence of cimetidine and clotrimazole. Kinetic analysis revealed a non-competitive mode of inhibition (Ki = 21 mM, cimetidine; Ki = 13 microM, clotrimazole). Reverse transcriptase-PCR and immunoblot analysis revealed no significant change in steady state levels of iNOS mRNA and protein expression with P-450IIIA inhibition. Purified iNOS enzyme activity was not altered. These data suggest that cytokine-mediated hepatocyte synthesis of NO is dependent upon P-450IIIA activity, which functions in a post-translational capacity.
...
PMID:Cytokine-mediated production of nitric oxide in isolated rat hepatocytes is dependent on cytochrome P-450III activity. 753 5

Cytokines, in particular IFN-gamma and IL-12, are important in host protection against infection with Toxoplasma gondii. This parasite is a major cause of congenital infection and morbidity in immunosuppressed persons, especially those with AIDS. IL-7, a monomeric protein produced by bone marrow stromal cells and fetal thymus, is able to induce the proliferation of pro-B cells and CD4+ and CD8+ T cells, and to enhance cytotoxicity of CTL and NK cells. Inbred mice were infected with a lethal dose of T. gondii and given IL-7 twice daily. Mice treated with IL-7 beginning at the time of infection survived, whereas mice either treated after infection or not treated died. Phenotypic analysis of splenocytes identified an expansion of NK (asialo GM1+) cells and CD8+ T cell populations. In vivo depletion of NK (asialo GM1+) and CD8+ T cells showed that cells expressing these phenotypes were important for maintaining protection against the parasite. IFN-gamma depletion resulted in complete reversal of the protective effect of IL-7 administration. In vivo depletion of endogenous IL-7 enhanced susceptibility to infection. Cytokine analysis by semiquantitative reverse-transcriptase PCR showed that IL-7 enhances the IFN-gamma response and furthermore reverses the parasite-mediated down-regulatory response on IL-2. These observations indicate that exogenous administration of human rIL-7 is able to protect mice against acute parasite challenge by stimulating IFN-gamma production and augmenting the CD8+ T cell-mediated CTL response.
...
PMID:IL-7 stimulates protective immunity in mice against the intracellular pathogen, Toxoplasma gondii. 759 82

Using a functioning rat thyroid cell line (FRTL-5), we studied the effects of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) on thyroidal type I iodothyronine 5'-deiodination (I-5'-deiodination) and on the expression of I-5'-deiodinase (I-5'-D) mRNA. After 24 h incubation in medium containing 0.5 microM rT3 with a tracer amount of [125I]rT3, radioactivity of released 125I- was counted. Deiodination in live FRTL-5 cells was enhanced about three times from the basal level by the addition of TSH and was inhibited markedly by propylthiouracil and dose dependently by T4. These results suggest the suitability of this model for investigating I-5'-deiodination in live thyroid tissue. Basal and TSH-induced I-5'-deiodination were significantly inhibited by 100 ng/liter of IL-1 beta and IL-6, and the inhibitory effect of TNF-alpha was seen over 1 microgram/liter. I-5'-deiodination was restored by removal of the cytokines. TSH-induced cAMP production and (Bu)2cAMP-induced I-5'-deiodination were also inhibited by the cytokines. Catalase, dexamethasone, and indomethacin did not abolish the inhibitory effects of the cytokines. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a marked suppression of I-5'-D mRNA expression by IL-1 beta and IL-6. We conclude that these cytokines inhibit the thyroidal type I I-5'-deiodination in the order of potency IL-1 beta > IL-6 >> TNF-alpha, probably by decreasing the I-5'-D mRNA level.(ABSTRACT TRUNCATED AT 250 WORDS)
J Interferon Cytokine Res 1995 Apr
PMID:Effects of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 on type I iodothyronine 5'-deiodination in rat thyroid cell line, FRTL-5. 762 12

A novel immunomodulator, imiquimod, has been shown to be an effective topical antiviral and antitumor agent in animal models. Imiquimod has been reported to induce interferon-alpha and other cytokines in animals and humans, but its precise role as an immunomodulator at skin sites has not been determined. We investigated its effect on cytokine gene expression in the human epidermal carcinoma cell line COLO-16 and human keratinocytes. COLO-16 cells were incubated with imiquimod (1 and 10 micrograms/ml) and human keratinocytes with 5 micrograms/ml for 6 or 24 h. Cytokine gene expression was analyzed by reverse-transcriptase PCR. In COLO-16 cells, imiquimod stimulated IL-6 mRNA levels 2.3- and 4.4-fold at 1 and 10 micrograms/ml after 6 h. IL-8 mRNA increased 4-fold at both 1 and 10 micrograms/ml. At 24 h, though IL-6 mRNA level at 1 micrograms/ml was further stimulated, enhanced expressions of IL-8 at 1 micrograms/ml and both IL-6 and IL-8 at 10 micrograms/ml were down-regulated. In human keratinocytes, 5 micrograms/ml of imiquimod stimulated IL-6 mRNA levels 1.4-fold at 6 h and 2.1-fold at 24 h, and IL-8 mRNA levels 1.7- and 2.0-fold at 6 and 24 h. IL-1 alpha mRNA levels in COLO-16 or keratinocytes were unchanged by either dose or incubation time. These results suggest that stimulation of IL-6 and IL-8 expression may be involved in the immunomodulating action of imiquimod.
Lymphokine Cytokine Res 1994 Apr
PMID:Effects of a novel topical immunomodulator, imiquimod, on keratinocyte cytokine gene expression. 806 Nov 17

Cytokine gene expression in peripheral blood mononuclear cells during the development of graft-versus-host disease (GVHD) in patients who underwent allogeneic bone marrow transplantation (allo BMT) was analysed using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of interleukin (IL)-1 beta, IL-6, and tumour necrosis factor (TNF)-alpha mRNA was increased during the development of GVHD and the degree of this increment depended on the severity of the disease. IL-2 expression was not detected at all and interferon-gamma expression was not much changed during GVHD. In patients with hepatic veno-occlusive disease (VOD), another transplantation-related complication, the expression of IL-1 beta and TNF-alpha mRNA was increased but IL-6 mRNA expression showed little increase. These findings suggest that IL-1 beta, IL-6 and TNF-alpha produced by peripheral blood mononuclear cells play an important role in the development of GVHD. Furthermore, liver dysfunction due to GVHD or VOD may be distinguishable by this type of cytokine analysis. Analysis of cytokine mRNA expression in peripheral blood mononuclear cells after allogeneic bone marrow transplantation may provide important information concerning the immune response and the cytokine network system in marrow transplant patients.
...
PMID:Cytokine gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation. 813 79

Cytokine production by T cells in the cerebrospinal fluid (CSF) and central nervous system (CNS) of SJL/J mice during myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) was examined. Reverse transcriptase/polymerase chain reaction (RT/PCR) was used to measure interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) mRNA levels from perfused CNS tissue (brain and spinal cord) and from cells isolated from CSF. Animals were grouped according to EAE severity, ranging from asymptomatic (adjuvant only) to severe disease (paralysis or severe paresis). Cytokine signals, normalized to actin, were almost undetectable in control tissues, and only slightly elevated in whole CNS tissue from animals with mild EAE. Both cytokine messages were strongly upregulated in CNS tissues derived from severely affected animals, consistent with previous observations correlating disease progression with infiltration by memory/effector CD4+ T cells, the major source of these cytokines. This cytokine upregulation was specific to the CNS, since other organs from the same animals did not express significant levels of IL-2 and IFN-gamma. CSF was obtained from the cisterna magna of unperfused mice and verified as such by absence of red blood cells (RBCs) and by immunoglobulin concentration orders of magnitude lower than in serum. Cytokine message was measured in RNA isolated from cells in CSF. Levels of IL-2 and IFN-gamma mRNA in CSF cells were significantly elevated in mild EAE and strongly upregulated in severe disease, correlating with those in total CNS tissue. These results confirm the CSF as representative of the immune status of the CNS and indicate a role for IL-2 and IFN-gamma in inflammatory CNS disease.
...
PMID:Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice. 829 48

A new immunomodulating agent, imiquimod, has been reported to have antiviral and antitumor activities in animal models. S-28463 (4-amino-2-ethoxymethyl-alpha, alpha-dimethyl-1H-imidazo[4, 5-c]quinoline-1-ethanol), an analog of imiquimod, has more potent antiviral activity in animals than imiquimod. It has also been shown to be more potent at inducing cytokines in human blood in vitro. However, its precise role as an immunomodulator in the skin has not been determined. We investigated the effect of S-28463 on human keratinocyte (KC) production of interferon-alpha (IFN-alpha) and other proinflammatory cytokines, including interleukin (IL)-1alpha, IL-8, and tumor necrosis factor-alpha (TNF-alpha). Human KC were incubated with S-28463 at two concentrations (1 microgram/ml and 10 micrograms/ml) for 6 h. Cytokine gene expression was analyzed by reverse-transcriptase PCR. In human KC, S-28463 stimulated significant increases in IFN-alpha mRNA at both concentrations. IL-1alpha mRNA increased 1.4-fold at 10 micrograms/ml. IL-8 mRNA was upregulated 2.5-fold at 10 micrograms/ml. Twenty-four hours after treatment, IL-1 alpha, IL-8, and TNF-alpha protein were increased, but IFN-alpha was below the level of detection. These results suggest that in the skin, S-28463-induced-IL-1 alpha, IL-8, and TNF-alpha production may be involved in the immunomodulating action of S-28463.
J Interferon Cytokine Res 1996 Jul
PMID:Effect of a novel topical immunomodulator, S-28463, on keratinocyte cytokine gene expression and production. 883 22

Semliki Forest virus (SFV) infection of mice is used as a model to study pathogenic processes occurring in viral encephalitis and demyelinating disease. In this study, the long-term effects of infection by the avirulent M9 mutant of SPV on the central nervous system (CNS) of BALB/c and SJL mice were determined. The presence of infectious virus, viral RNA and cytokine mRNA in the brains of individual mice and the presence of lesions in the spinal cords of the same mice up to 360 days post-infection (d.p.i.) were analysed in order to detect any correlation between these parameters of pathogenesis. Infectious virus could not be detected beyond 7 d.p.i. for either mouse strain. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the presence of the E2 and nsP1 regions of the virus genome and mRNA for interferon-gamma and tumour necrosis factor-alpha. Viral RNA could be detected up to 90 d.p.i. for both mouse strains. Cytokine mRNA could be detected up to 28 d.p.i. for BALB/c mice but up to 360 d.p.i. for SJL mice. Inflammatory lesions, which were associated with cytokine mRNA expression, were not detected in BALB/c mice beyond 28 d.p.i. but were detected in two SJL mice at 90 d.p.i. It is concluded that M9-SFV infection induces long-term prolonged expression of pro-inflammatory cytokines in the CNS of the majority of SJL (but not BALB/c) mice which is not associated with persistence of the virus genome. M9-SFV infection of SJL mice may be a relevant model for the pathogenesis of multiple sclerosis in man.
...
PMID:Long-term effects of Semliki Forest virus infection in the mouse central nervous system. 922 33

Cytokine-driven activation of hepatic stellate cells (HSC) in tissue injury and inflammation is a key pathogenetic event in liver fibrogenesis leading to an expanded pool of matrix producing myofibroblasts (MFB) which represent the transformed counterpart of HSC. We hypothesize that expansion of the pool of MFB might also be accomplished by modulation of apoptosis, which plays an opposite and complementary role to mitosis in the cellular homeostasis. We characterized the susceptibility of HSC in primary culture and of MFB in secondary culture to apoptosis induced by the soluble Fas ligand (sFasL) and related the effects to the expression levels of Fas (APO-1/CD95) and some major proapoptotic and contra-apoptotic protooncogenes. MFB showed a dose-dependent apoptotic reaction upon exposure to sFasL as evidenced by a strong increase of nucleosomal DNA fragments, loss of cellular DNA, positive TUNEL reaction, and annexin staining. The effect was found only if protein synthesis (cycloheximide) or RNA synthesis (actinomycin D) were arrested. HSC maintained for various times in primary culture were completely resistant to sFasL in combination with cycloheximide, but in late primary cultures (day 7 onward) an increasing susceptibility to sFasL-mediated apoptosis was developed. By semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis and alkaline phosphatase-anti-alkaline phosphatase staining Fas receptor was identified both in HSC and MFB at comparable expression levels. The expression of the contra-apoptotic protooncogenes bcl-2 and bcl-xl was found to be much stronger in early HSC than in late HSC and MFB as shown by ribonuclease protection assay. The expression of bcl-2 was additionally confirmed by semiquantitative RT-PCR and immunoblotting. Proapoptotic bax was found in comparable quantities at the RNA level in HSC and MFB but at the protein level MFB showed increased bax expression. It is concluded that transformation of HSC to MFB is paralleled by an increasing sensitivity to sFasL-mediated apoptosis, which might be related to a strong decrease of bcl-2 and bcl-xl expression, leading to a preponderance of proapoptotic gene expression in MFB. Modulation of apoptotic susceptibility of transforming HSC could be an important complementary pathway in the pathogenesis of fibrosis.
...
PMID:Transformation-dependent susceptibility of rat hepatic stellate cells to apoptosis induced by soluble Fas ligand. 969 16

Estrogen supplements are the primary pharmacologic intervention therapy to prevent and treat loss of bone mass (osteoporosis) in postmenopausal women. Furthermore, at sites of local inflammation near bone, estrogen-deficient women are significantly more susceptible to bone loss than are estrogen-sufficient women. In the present study, we investigate whether estrogen modulates osteoblast (MG-63) production of interleukin-6 (IL-6), an osteoclast recruitment and differentiation of cytokine, in the presence of the proinflammatory cytokine, IL-1beta. Using enzyme-linked immunosorbent assay (ELISA), we demonstrate that IL-1beta significantly enhances IL-6 secretion into culture supernatants in a dose-dependent and time-dependent manner. Using reverse-transcriptase polymerase chain reaction (RT-PCR) and ELISA respectively, we demonstrate further that levels of 17beta-estradiol (active metabolite of estrogen) > or = those found in serum of estrogen-sufficient women inhibit steady-state IL-6 mRNA levels as well as inhibit secretion of IL-6 into culture supernatants. One mechanism by which estrogen therapy preserves bone mass in areas of inflammation may be via inhibition of IL-1beta-stimulated obsteoblast-derived IL-6.
J Interferon Cytokine Res 1998 Jul
PMID:Estrogen inhibits interleukin-1beta-induced interleukin-6 production by human osteoblast-like cells. 971 63


1 2 3 4 Next >>

---