Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of the constitutive nitric oxide (NO) in the expression of interferon (IFN) genes in mouse peritoneal macrophages (PM). The treatment of PM with L-arginine-N(G)-amine (AA), a potent inhibitor of NO-producing enzymes, resulted in a marked accumulation of IFN-alpha4 mRNA and, to a minor extent, of IFN-beta mRNA. In contrast, the expression of IFN-gamma mRNA, as well as tumor necrosis factor alpha and interleukin-6 mRNA, was not affected. Furthermore, a remarkable increase in the expression of the IFN regulating factor 1 (IRF-1), but not of IRF-2, mRNA was detected in AA-treated PM. To investigate whether the AA-induced activation of the IFN system correlates with the production and antiviral activity of IFN, the extent of encephalomyocarditis virus (EMCV) replication was monitored in AA-treated PM with respect to control cultures. AA treatment strongly inhibited, in a dose-dependent manner, EMCV yields in PM. Likewise, similar results were obtained by the addition of the NO-scavenger carboxyphenyl-tetramethylimidazoline-oxyl-oxide. In addition, inhibition of NO synthesis by N(G)-mono-methyl-L-arginine in PM strongly decreased virus replication in coculture of PM and EMCV-infected L929 cells, whereas no antiviral effect was observed in L929 cells alone. Moreover, the AA-mediated antiviral activity was abrogated in the presence of antibody to IFN-alpha/beta, whereas antibody to IFN-gamma was completely ineffective. Taken together, these results indicate that low levels of NO, constitutively released by resting PM, negatively regulate the expression and activity of IFN-alpha/beta in PM. We suggest that NO acts as a homeostatic agent in the regulation of IFN pathway expression in macrophages.
 ...
PMID:Inhibitory activity of constitutive nitric oxide on the expression of alpha/beta interferon genes in murine peritoneal macrophages. 1043 21

The acute effects of a i.m. injection of interferon beta-1a on the secretion of the cytokines interleukin-6, tumor necrosis factor-alpha, soluble tumor necrosis factor receptor I, and interleukin-1 receptor antagonist and its relation to peripheral concentrations of adrenocorticotropic hormone (ACTH) and cortisol in patients with MS were investigated, as well as the influence of cotreatment with indomethacin on these parameters. After interferon beta injection we found an acute rise in plasma cytokine levels and an increase in plasma hormone concentrations, both of which were modulated by indomethacin comedication.
 ...
PMID:Acute effects of interferon beta-1a on plasma cytokine levels in patients with MS. 1107 9

Multiple sclerosis (MS) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system, associated with an altered cytokine network. We previously assayed peripheral blood T-lymphocyte binding for two prototypic cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and found that T cells from MS patients had significantly more TNF-alpha and IL-6 receptors than those from healthy controls. In the present work, paralleling a previous one on T-cell TNF-alpha binding, we studied the effect of interferon (IFN)-beta-1b treatment on T-lymphocyte IL-6 binding in patients with relapsing-remitting MS. T cells from MS patients had significantly (P < 0.001) higher amounts of IL-6 receptors than those from controls [292 +/- 6 vs. 228 +/- 8 (mean +/- SEM) receptors per cell, respectively], whereas the ligand-receptor affinity values were similar in the two groups [26.2 +/- 0.7 and 25.7 +/- 0.4 (mean +/- SEM) pmoles/l, respectively]. After a 3-month IFN-beta-1b treatment, they showed a significant decrease in IL-6 binding [266 +/- 7 (mean +/- SEM) receptors per cell]. After 6 and 9 months, T-cell IL-6 B(max) values were even lower [258 +/- 8 and 251 +/- 8 (mean +/- SEM) receptors per cell]. Since an increased IL-6 binding might be linked to a lymphocyte activation, our data give further support for an enhanced immune response in patients with MS. Our data seem to demonstrate that the major effects of IFN-beta-1b treatment result in a decrease of T-cell activation.
 ...
PMID:T-cell interleukin-6 receptor binding in interferon-beta-1b-treated multiple sclerosis patients. 1113 50

Recent evidence suggests that CD38, an ectoenzyme that converts NAD(+) to cyclic ADP-ribose (cADPr), may play a role in cytokine-induced airway smooth muscle (ASM) cell hyper-responsiveness, a key feature associated with chronic asthma. In the present study, we investigated the major signaling pathways by which tumor necrosis factor-alpha (TNFalpha) induces CD38 expression and its role in regulating gene expression in human ASM cells. Using flow cytometry analyses, TNFalpha enhanced CD38 expression in a manner that was time-(0-24 h), concentration-(0.1-40 ng/ml), and protein synthesis-(cycloheximide blockade) dependent. A selective agonistic antibody against tumor necrosis factor receptor (TNFR) 1 also augmented CD38 expression, whereas anti-TNFR2 antagonistic antibody did not prevent the TNFalpha response. Inhibition of the Janus activated kinase/signal transducer and activator of transcription pathways using the soluble inhibitor 2-(1,1-dimethylethyl)-9-fluoro-3,6-dihydro-7H-benz-[h]imidaz[4,5-f]isoquinolin-7-one (DBI) or with neutralizing antibody against interferon beta (IFNbeta) completely abrogated TNFalpha-induced CD38 expression at both protein and mRNA levels. Combining TNFalpha (0.1 and 1 ng/ml) and IFNbeta (100 IU/ml) at concentrations alone that had little effect on CD38 expression induced a robust synergistic induction of CD38 mRNA and protein levels. 8-Bromo-cADPr, a cADPr antagonist, significantly augmented TNFalpha-induced interleukin-6 secretion, whereas regulated on activation normal T cell expressed and secreted secretion was suppressed. 8-Bromo-cADPr, however, did not affect TNFalpha-induced cell surface expression of intercellular adhesion molecule-1. Our study is the first to demonstrate that IFNbeta-dependent activation of CD38 pathway is a novel component by which TNFalpha differentially regulates the expression of inflammatory genes in ASM cells.
 ...
PMID:Tumor necrosis factor-alpha differentially regulates the expression of proinflammatory genes in human airway smooth muscle cells by activation of interferon-beta-dependent CD38 pathway. 1526 23

Lassa virus (LV) and Mopeia virus (MV) are closely related members of the Arenavirus genus, sharing 75% amino acid sequence identity. However, LV causes hemorrhagic fever in humans and nonhuman primates, whereas MV cannot induce disease. We have previously shown that antigen-presenting cells (APC)-macrophages (MP) and dendritic cells (DC)-sustain high replication rates of LV but are not activated, suggesting that they play a role in the immunosuppression observed in severe cases of Lassa fever. Here, we infected human APC with MV and analyzed the cellular responses induced. MV infection was productive in MP and even more so in DC. Apoptosis was not induced in either cell type. Moreover, unlike DC, MP were early and strongly activated in response to MV, as shown by the increased surface expression of CD86, CD80, CD54, CD40, and HLA-abc and by the production of mRNA encoding alpha interferon (IFN-alpha), IFN-beta, tumor necrosis factor alpha and interleukin-6. In addition, MV-infected MP produced less of the virus than DC, which was related to the fact that these cells secreted IFN-alpha. Thus, the strong activation of MP is probably a major event in the control of MV infection and may be involved in the induction of an adaptive immune response in infected hosts. These results may explain the difference in pathogenicity between LV and MV.
 ...
PMID:Human macrophages, but not dendritic cells, are activated and produce alpha/beta interferons in response to Mopeia virus infection. 1536 18

Cytokines play an important role in the onset, regulation, and propagation of immune and inflammatory responses within the central nervous system (CNS). The main source of cytokines in the CNS are microglial cells. Under inflammatory conditions, microglial cells are capable of producing pro- and antiinflammatory cytokines, which convey essential impact on the glial and neuronal environment. One paramount functional feature of astrocytes is their ability to form a functionally coupled syncytium. The structural link, which is responsible for the syncytial behavior of astrocytes, is provided by gap junctions. The present study was performed to evaluate the influence of inflammation related cytokines on an astroglial/microglial inflammatory model. Primary astrocytic cultures of newborn rats were cocultured with either 5% (M5) or 30% (M30) microglial cells and were incubated with the following proinflammatory cytokines: tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and the antiinflammatory cytokines transforming growth factor-beta1 (TGF-beta1) and IFN-beta. Under these conditions, i.e., incubation with the inflammatory cytokines and the high fraction of microglia (M30), microglial cells revealed a significant increase of activated round phagocytotic cells accompanied by a reduction of astroglial connexin 43 (Cx43) expression, a reduced functional coupling together with depolarization of the membrane resting potential (MRP). When the antiinflammatory mediator TGF-beta1 was added to proinflammatory altered M30 cocultures, a reversion of microglial activation and reconstitution of functional coupling together with recovery of the astroglial MRP was achieved. Finally IFN-beta, added to M5 cocultures was able to prevent the effects of the proinflammatory cytokines TNF-alpha, IL-1beta, and IFN-gamma.
 ...
PMID:Effects of cytokines on microglial phenotypes and astroglial coupling in an inflammatory coculture model. 1592 Jul 25

A woman with a menstrual cycle-dependent fever (more than 38 degrees C) and severe fatigue that disrupted her ability to work was referred to our hospital. Six years ago, the patient received interferon beta injections (6,000,000 IU day-1x48 days) for the treatment of hepatitis C virus. Although the treatment was successful against the virus, the symptomatic fever occurred monthly since the third year after receiving the treatment. The symptoms occurred a few days after ovulation in every menstrual cycle. When the ovarian function was suppressed by GnRH agonist (GnRHa), the symptoms disappeared. While in anovulation, the patient received estrogen followed by estrogen with progestogen, which resembles the sex hormone milieu of a normal menstrual cycle without the LH surge; this treatment did not induce the symptoms. When human CG (hCG) was injected on the beginning day of estrogen with progestogen following treatment with estrogen alone, the previous symptoms reappeared. However, the hCG injection without estrogen priming did not induce the symptoms. These studies indicated that the LH surge after estrogen priming induced the symptoms. Changes in serum inflammatory cytokine levels (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) were examined during the ovulatory cycle and the interleukin-1 levels during the treatment. There were no significant changes on these levels in the febrile period. The patient experienced normal menstrual cycles after finishing the five-month GnRHa treatment. Although her symptoms still occur, they are mild and do not require further medical treatment.
 ...
PMID:A case of ovulatory cycle-dependent symptoms in woman with previous interferon beta therapy. 1600 34

Leptin is a peptide hormone which acts on cells of immune system by influencing the production of cytokines. Serum leptin levels and cytokine production by peripheral blood mononuclear cells (PBMC) were measured in 18 secondary progressive multiple sclerosis (SPMS) patients under IFN-beta-1b treatment. There were no overall effects on leptin, interleukin-6 (IL-6), IL-10 and IL-12 p40 after 2, 6 and 12 months of treatment. However, leptin and IL-6 decreased after 6 and 12 months of treatment in 12 patients who did not show progression of disability. Thus, our pilot data show that the beneficial effect of IFN-beta on some SPMS patients might be associated with the reduced levels of leptin and reduced IL-6 production by PBMC.
 ...
PMID:Evidence of involvement of leptin and IL-6 peptides in the action of interferon-beta in secondary progressive multiple sclerosis. 1626 54

The Kaposi's sarcoma-associated herpesvirus (KSHV) envelope glycoprotein gpK8.1 contributes to cellular attachment through binding cell surface heparan sulfate proteoglycans. By using a soluble recombinant form of gpK8.1, we discovered that a consequence of gpK8.1 interaction with human fibroblasts is the induction of an antiviral response, as characterized by the activation of interferon regulatory factor 3 (IRF-3), production of interferon beta (IFN-beta), and expression of interferon-stimulated antiviral genes. In contrast, neither IFN-beta expression nor a functional antiviral response is observed in cells treated with KSHV virions. The interferon response induced by soluble gpK8.1 can be inhibited by simultaneous treatment with UV-inactivated virions, while the induction of an indicator inflammatory cytokine, interleukin-6, was readily evident in the response to both gpK8.1 and KSHV. In addition, KSHV virions abrogate gpK8.1-mediated activation of IRF-3, an early transcriptional regulator for cellular antiviral responses. Although innate immune responses are initiated during contact between gpK8.1 and cellular receptor(s), these results suggest that the virion contains one or more structural elements that selectively repress an effective antiviral response while allowing cellular responses favorable to the KSHV life cycle.
 ...
PMID:Kaposi's sarcoma-associated herpesvirus virions inhibit interferon responses induced by envelope glycoprotein gpK8.1. 1695 42

Proinflammatory cytokines are known to impair intestinal barrier function and to activate signaling pathways, whereas heat shock responses prevent cytokine-induced mucosal damage. We hypothesized that heat shock response blocks the effects of proinflammatory cytokines by regulating nitric oxide (NO) production and the activities of the Janus kinase/signal transducer and activator of transcription (STAT) pathway. A monolayer of Caco-2 cells were pretreated with sodium arsenite (SA, 500 micromol/L) for 1 h, followed by a 1-h recovery, and then stimulated with a cytokine mixture (cytomix: tumor necrosis factor alpha [10 ng/mL], interferon beta [1000 U/mL], and interleukin [IL] 1beta [1 ng/mL]) for 24 h. The permeability of horseradish peroxidase and fluorescein isothiocyanate-conjugated Dextran and transepithelial resistance and potential difference were measured in Ussing chambers. Interleukin-6, IL-8, NO, inducible NO synthase mRNA, STAT activity, and suppressor of cytokine signaling (SOCS) expression were measured in medium or cell lysates. Cytomix resulted in increased epithelial permeability of both fluorescein isothiocyanate-conjugated Dextran and horseradish peroxidase; whereas treatment of Caco-2 cells with SA 500 micromol/L blocked the cytomix-induced permeability changes. In addition, SA treatment decreased cytomix-induced NO production and inducible NO synthase mRNA expression and decreased the levels of STAT1, STAT3, SOCS1, and SOCS3. The SA treatment also decreased cytomix-induced IL-6 and IL-8 production in a dose-dependent manner. In conclusion, cytomix increased epithelial permeability, which is associated with increased NO and STAT activities. The SA treatment ameliorated cytomix-induced permeability, possibly through the downregulation of the NO and Janus kinase/STAT pathways.
 ...
PMID:Heat shock stress ameliorates cytokine mixture-induced permeability by downregulating the nitric oxide and signal transducer and activator of transcription pathways in Caco-2 cells. 1722 93


<< Previous 1 2 3 4 5 6 7 Next >>