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)

Flavone-8-acetic (FAA) acid is a potential chemotherapeutic agent that has demonstrated strong immunomodulatory activity in murine model systems. The immunomodulatory activity of this drug in murine systems has been linked to its ability to rapidly induce cytokine gene expression in vivo and in mouse splenocytes ex vivo. We have now developed a tissue culture model for studying the molecular basis of induction of cytokine expression by FAA. Using the mouse macrophage cell line, ANA-1, we can demonstrate the direct induction of interferon beta (IFN beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), and interferon response factor-1 (IRF-1) mRNA expression following treatment with FAA. Furthermore, the induction of the IFN beta mRNA can occur in the absence of new protein synthesis. Nuclear run-on experiments indicate that at least part of the induction of IFN beta, IL-6, and TNF alpha mRNA occurs at the transcriptional level while the increase in IRF-1 mRNA appears largely post-transcriptional or due to the production of IFN beta protein. Additionally, experiments using agents that interfere with second messengers demonstrate that activation of the protein kinase C pathway is possibly involved in FAA gene induction. The use of this tissue culture model system should lead to a more complete understanding of the mechanisms involved in FAA-induced gene expression and help determine why this drug is inactive on human cells.
 ...
PMID:Induction of multiple cytokine gene expression and IRF-1 mRNA by flavone acetic acid in a murine macrophage cell line. 803 45

The effects of interleukin-6 (IL-6) on interferon regulatory factor 1 (IRF-1) gene expression were studied in B-hybridoma B9 cells which are growth-stimulated by IL-6 and breast carcinoma T47D cells which are growth-inhibited. IL-6 induced the production of IRF-1 mRNA and protein in both cell types, but IRF-1 binding activity to its target DNA sequence was induced only in T47D cells. With B9 cells, there was no IRF-1 binding but instead strong constitutive binding of the IRF-2 repressor, indicating that binding of IRF-1 to DNA is an important regulatory step. The IRF-1 gene promoter element, palindromic IFN-response element (pIRE), was found to respond to IL-6 with high efficiency as compared with IFN-gamma or IFN-beta. On this palindromic TTC...GAA sequence, two protein complexes (pIRE-a and pIRE-b) were induced within minutes by IL-6. pIRE-b is similar to the main complex induced by IFN-gamma and contains the Stat91 protein. pIRE-a predominantly induced by IL-6 is a slowly migrating complex which does not contain Stat91 and has low affinity for IFN-gamma activated sequence (GAS)-type sequences. Comparison of the relative effects of IL-6 and IFN-gamma shows that pIRE enhancers are differently regulated than GAS elements. Distinct transcription complexes, forming in ratios dependent on the inducer, help explain how various cytokines sharing effects through Stat91 on related enhancers can produce specific patterns of gene expression. Activation of the pIRE-a factors defines a novel transcriptional activity of IL-6 in epithelial and lymphoid cells.
 ...
PMID:Induction by interleukin-6 of interferon regulatory factor 1 (IRF-1) gene expression through the palindromic interferon response element pIRE and cell type-dependent control of IRF-1 binding to DNA. 816 91

Immunocytochemical staining of spinal cords from five autopsied patients with HTLV-I-associated myelopathy/tropical spastic paraparesis was performed using a panel of monoclonal or polyclonal antibodies reactive with interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-beta, IFN-gamma and transforming growth factor (TGF)-beta. In the spinal cords of patients with a shorter duration of illness, IL-1 beta, TNF-alpha, and IFN-gamma were expressed on perivascular infiltrating macrophages, astrocytes and microglia in active-chronic inflammatory lesions. In striking contrast, we rarely noted cytokine expression except for IFN-gamma in inactive-chronic lesions of patients with longer durations. In situ expression of these cytokines on microglia and astrocytes, in addition to infiltrating mononuclear cells, suggests that glial cells participate in the inflammatory process, especially in active lesions. In addition, the cytokine expression was gradually downregulated along with duration of illness.
 ...
PMID:Cytokine expression in the spinal cord lesions in HTLV-I-associated myelopathy. 830 22

Lipopolysaccharide treatment of mouse macrophage-like J774 cells was found to result in the activation of three different nuclear proteins which specifically bind to oligonucleotide containing the NF-kappa B motif of the human immunodeficiency virus (HIV) gene. These are designated as NF-kappa B1, -kappa B2, and -kappa B3, according to their electrophoretic mobilities (fast, intermediate, and slow, respectively). Immunological and UV cross-linking studies showed that NF-kappa B1 consists of only p50 subunit, whereas both NF-kappa B2 and -kappa B3 contain NF-kappa B p65 subunit and c-Rel. In addition, NF-kappa B2 was also found to contain p50 subunit of NF-kappa B. The binding of three types of NF-kappa B proteins to HIV NF-kappa B motif was effectively inhibited by other NF-kappa B motifs, whose 3' half-site nucleotide sequences are T/A-T-T/C-CC (HIV, interleukin-6, interferon (INF)-beta, H2-Kb, I-E alpha d, and TNF-alpha 2 (nucleotide position -510)) and much less effectively by NF-kappa B motifs with 3' half-site sequences of TGCCC (TNF-alpha 3, nucleotide position -610), ATCTC (G-CSF), TATTC (Fc gamma R), or TCCTT (TNF-alpha 1, nucleotide position -850). Our data also suggested that NF-kappa B1 and -kappa B2 which contain p50 subunit of NF-kappa B bind with the higher preference for NF-kappa B motif of H2-Kb gene promoter than that of INF-beta, whereas NF-kappa B3 which does not contain p50 subunit appears to preferentially bind to NF-kappa B sites of IFN-beta.
 ...
PMID:Influence of 3' half-site sequence of NF-kappa B motifs on the binding of lipopolysaccharide-activatable macrophage NF-kappa B proteins. 836 97

Type I interferons (IFNs-alpha and IFN-beta) bind to a common receptor to exert strong antiproliferative activity on a broad range of cell types, including interleukin-6 (IL-6)-dependent myeloma cells. In this study, we investigated the effect of IFN-beta pretreatment on IL-6-stimulated mitogenic signaling in the human myeloma cell line U266. IL-6 induced transient tyrosine phosphorylation of the IL-6-receptor signal-transducing subunit gp130, the gp130-associated protein tyrosine kinases Jak1,Jak2, and Tyk2, the phosphotyrosine phosphatase PTP1D/Syp, the adaptor protein Shc and the mitogen-activated protein kinase Erk2, and accumulation of GTP-bound p21ras. Prior treatment of U266 cells with IFN-beta downregulated IL-6-induced tyrosine phosphorylation of gp130, Jak2, PTP1D/Syp, Shc, and Erk2, and GTP-loading of p21ras. Further analysis indicated that treatment with IFN-beta disrupted IL-6-induced binding of PTP1D/Syp to gp130 and the adaptor protein Grb2; IFN-beta pretreatment also interfered with IL-6-induced interaction of Shc with Grb2 and a 145-kD tyrosine-phosphorylated protein. These results suggest a novel mechanism whereby type I IFNs interrupt IL-6-promoted mitogenesis of myeloma cells in part by preventing the formation of essential signaling complexes leading to p21ras activation.
 ...
PMID:Interferon-beta interrupts interleukin-6-dependent signaling events in myeloma cells. 897

Human hydatidosis is a parasitic disease vectored by the larval stage cestode Echinoccocus granulosus. It constitutes a major health problem in North Africa. We investigated the production of circulating interferon (IFN), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in Algerian patients with liver, lung, or ocular hydatidosis. In all, 101 serum samples from these patients with analyzed. Immunoreactivity and cytokine activities were undetectable in sera from ocular hydatidosis patients. However, we observed the presence of IFN (a mixture of IFN-alpha, IFN-beta, and IFN-gamma, range 32-500 U/ml), TNF-alpha (range 32-100 U/ml), and IL-6 (range 32-500 U/ml) in all patients who had liver or lung cysts or both and displayed immunoreactivity against parasitic antigen (antigen 5). After surgical removal of the cysts, serum cytokine levels declined rapidly and were undetectable at 30 days. IFN and IL-6 activity was undetectable in sera from two liver hydatidosis patients who relapsed and did not display any immune response against parasitic antigen. These results suggest that in liver and lung hydatidosis, cytokine production contributes to the host defense mechanism against the extracellular parasite.
 ...
PMID:Relationship among circulating interferon, tumor necrosis factor-alpha, and interleukin-6 and serologic reaction against parasitic antigen in human hydatidosis. 914 50

Interferons (IFNs) originally described for antiviral activity have been reported to have pleiotropic effects, including the ability to induce interleukin-6 (IL-6) and IL-8 production in several cell types. IL-6 and IL-8 are proinflammatory cytokines and are known to be produced by a wide variety of cells, including human keratinocytes. In the present study, we sought to examine the effects of IFNs on IL-6 and IL-8 production from human keratinocytes. IFN-gamma (10-50 ng/ml) induced IL-6 and IL-8 production dose dependently, but no induction of IL-6 or IL-8 was observed with either IFN-alpha or IFN-beta. Because cytokines often work in a cascade fashion and keratinocytes are a source of primary cytokines, IL-1 alpha, and tumor necrosis factor-alpha (TNF-alpha), we examined whether combined treatment with IFN-gamma and these primary cytokines, IL-1 alpha and TNF-alpha, had a synergistic effect on the production of IL-6 and IL-8. Combined treatment with IFN-gamma and IL-1 alpha induced 6-fold to 7-fold higher levels of IL-6 than IL-1 alpha alone. Combined treatment with IFN-gamma and TNF-alpha induced 11-fold to 12-fold higher levels of IL-6 than TNF-alpha alone. The same treatment induced 3-fold to 4-fold higher levels of IL-8 in both cases. These results suggest that IFN-gamma is a positive regulator for the production of IL-6 and IL-8 from human keratinocytes and likely has an augmentative effect on skin inflammation.
 ...
PMID:Effects of interferons on the production of interleukin-6 and interleukin-8 in human keratinocytes. 919 2

We have studied the expression of cytokines and viral genes induced by Newcastle disease virus (NDV) and Sendai virus in bone marrow-derived macrophages (BMM) and lymphocytes from C57BL/6 mice and the congenic line B6.C-H-28c. These mice carry the loci If-1h (high) or If-1l (low), respectively, that are responsible for up to tenfold differences in the interferon (IFN)-alpha, IFN-beta, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) response to NDV but not to Sendai virus. Only BMM but not spleen lymphocytes showed allele-specific differences in NDV-induced cytokine levels, indicating cell-specific If-1 expression. The If-1 locus harbors IFN-inducible gene(s) whose expression is prevented in the presence of cycloheximide. Our data provide evidence that the If-1l allele acts by specifically suppressing the cytokine response to NDV. Cytokine production was dependent on infectious virions, and kinetic analyses revealed a close correlation between the amount of viral transcripts and individual cytokine mRNA. BMM from lf-1l mice strongly restricted transcription of the NDV nucleoprotein (NP) gene, whereas BMM from If-1h mice supported NP transcription. Following treatment with IL-4, which inhibited constitutive IFN-beta gene expression, however, If-1l BMM became highly permissive for transcription of the viral NP gene and released high amounts of cytokines. We conclude that If-1l gene products are responsible for the low producer phenotype by efficiently interfering with NDV transcription, leading to strongly reduced intracellular levels of cytokine inducing viral dsRNA intermediates.
 ...
PMID:Interferon-induced expression of If-1h and If-1l alleles in Newcastle disease virus-infected mouse macrophages is associated with specific differences in viral gene transcription. 955 81

Low-dose oral steroid use at the onset of interferon beta-1b (IFNbeta-1b) therapy in relapsing-remitting multiple sclerosis (RR-MS) patients reduces flulike symptoms. To determine the mechanism by which steroid treatment minimizes these side effects, we analyzed the percentage of interleukin-6 (IL-6)-, interferon-gamma (IFN-gamma)-, tumor necrosis factor alpha (TNF-alpha)-, and IL-10-producing cells before and after 3 months of IFNbeta-1b therapy onset. Our results support a relationship between IL-6 induction and fever. Such side effects can be ameliorated by steroids.
 ...
PMID:Amelioration of flulike symptoms at the onset of interferon beta-1b therapy in multiple sclerosis by low-dose oral steroids is related to a decrease in interleukin-6 induction. 977 68

To compare virological, biochemical, and immune responses to human lymphoblastoid interferon (IFN-alpha) and human fibroblast interferon (IFN-beta) in patients with chronic hepatitis C virus (HCV) infection, 120 patients were randomly assigned to three groups (group A, 60 patients receiving IFN-alpha, 6 million units (MU) once a day, daily for one month and thrice weekly for five months; group B, 40 patients receiving 6 MU IFN-beta once a day daily for two months; and group C, 20 patients receiving 3 MU IFN-beta twice a day (6 MU/day) daily for two months). Serum soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay. Patients with sustained clearance of serum HCV RNA detected by polymerase chain reaction (PCR) at six months after IFN treatment were defined as having complete response to IFN treatment. A low level of HCV RNA (< or = 10(4) copies/50 microl, measured by competitive PCR) and HCV RNA of genotype 2a were favorable factors for a complete response to both IFNs. Complete response in group A treatment was strongly associated with early HCV RNA clearance, in contrast with group B. A significantly higher HCV RNA negativity at the second week from start of treatment was noted in group C (80.0%), compared with groups A (41.6%) and B (27.5%). sIL-2R levels rose in each group during IFN administration. In group C, alanine aminotransferase (ALT) and IL-6 levels were remarkably elevated. These findings indicate that timing of serum HCV RNA negativity in sustained response differs between IFN-alpha and IFN-beta administrations and that early HCV RNA clearance was induced by twice-a-day IFN-beta treatment.
 ...
PMID:Differences between interferon-alpha and -beta treatment for patients with chronic hepatitis C virus infection. 1008 Jan 58


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