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)

The effects of direct activators of protein kinase C (PKC) (the phorbol ester tetradecanoyl phorbol myristic acid [TPA] or bryostatin) on the ability of a highly enriched population of granulocyte-macrophage colony-forming cells (GM-CFC) to proliferate and develop in soft agar was assessed. In the absence of colony stimulating factors, the PKC activators did not stimulate colony formation. However, in the presence of optimal concentrations of granulocyte colony-stimulating factor (G-CSF) or interleukin-6 (IL-6), TPA or bryostatin markedly elevated the number of colonies formed from the GM-CFC. In the absence of TPA, IL-6, and G-CSF, respectively, both stimulated the formation of about 3% of the colonies observed when IL-3 was present. When TPA plus G-CSF or IL-6 were added together, this figure increased to 48% and 54%, respectively. In both instances, the types of mature cells formed was altered from colonies of mature neutrophilic cells to a mixture consisting predominantly of macrophages with some neutrophils. Similar results were observed when bryostatin replaced TPA in these assays. When single cell colony-forming assays were performed, the same results were obtained. The presence of G-CSF, or IL-6, and the activator of PKC used (TPA or bryostatin) was required throughout the colony-forming assay for an optimal synergistic effect to be observed. These data indicate that agents that activate PKC can promote the proliferation and development of GM-CFC via a synergistic interaction with G-CSF or IL-6. Furthermore, there is an apparent role for PKC in development and possibly lineage commitment of GM-CFC.
 ...
PMID:Protein kinase C activators can interact synergistically with granulocyte colony-stimulating factor or interleukin-6 to stimulate colony formation from enriched granulocyte-macrophage colony-forming cells. 767 6

In previous studies, rat adrenal zona glomerulosa (ZG) cells were demonstrated to release interleukin-6 (IL-6). In the current study, cultures of ZG cells and bioassays for tumor necrosis factor (TNF) and IL-6 were used to determine if ZG cells release TNF and to define more fully the factors that regulate ZG IL-6 release. ZG cells released IL-6 and TNF, and this release was stimulated by lipopolysaccharide, interleukin-1 alpha, interleukin-1 beta, a protein kinase C activator, and a calcium ionophore without affecting intracellular adenosine 3', 5'-cyclic monophosphate (cAMP) content. In contrast, adrenocorticotropic hormone (ACTH) increased the intracellular cAMP content, increased basal and secretagogue-stimulated IL-6 release but decreased basal and secretagogue-stimulated TNF release. The effects of ACTH on IL-6 and TNF release may be mediated by increases in intracellular cAMP because ACTH and dibutyryl cAMP modified IL-6 and TNF release in an identical manner. Therefore, IL-6 and TNF release from ZG cells can be differentially regulated. Because IL-6 and TNF modify adrenal steroid release, the adrenal production of these cytokines may have a role in the stress response.
 ...
PMID:Differential release of tumor necrosis factor and IL-6 from adrenal zona glomerulosa cells in vitro. 784 Jan 68

A multiple immunodeficiency, involving antibody- and cell-mediated responses in 10 Chinese Shar-Pei (CSP) dogs is described. Abnormal levels of serum IgM and IgA in most cases, and IgG in fewer cases characterized the immunoglobulin deficiencies. Decreased in vitro proliferative responses of pokeweed mitogen (PWM)-stimulated peripheral blood mononuclear cells (PBMC) were found in nine cases. Clinical presentation involved several organ systems and was associated with recurrent infections and malignancy. Sera from affected dogs suppressed PWM-stimulated cell proliferation of affected and normal dogs, but not cultures stimulated with PWM followed by recombinant IL-2 (rIL-2). In vitro supplementation of PBMC cultures with immunomodulatory guanosine analogs (GA) resulted in increased de novo IgG and/or interleukin-6 (IL-6) synthesis. Cells from five immunodeficient dogs showed in vitro evidence of GA- or rIL-2-dependent enhanced immunological responses. Since rIL-2-mediated activation of the IL-2 receptor and GA-mediated immunomodulation are reported to act through protein kinase C (PKC)-independent pathways, it is concluded that the IL-2 receptor is functional in these dogs and that cell activation through alternative pathways may restore immune responses in affected CSP dogs.
 ...
PMID:A primary immunodeficiency syndrome in Shar-Pei dogs. 785 14

Colony formation of mouse primitive hemopoietic progenitors with interleukin-6 (IL-6) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and their signal transduction were studied. Although IL-6 or TPA alone could not form colonies, their combination gave rise to significant number of colonies from Day-2 post 5-FU bone marrow cells. When colony numbers were compared with those supported by IL-3, IL-6+TPA gave rise to 86 + 47% of colonies formed with IL-3. Time course of colony formation with IL-6+TPA run parallel with that of IL-3. These colonies included not only granulocyte/macrophage (GM) colonies, but also granulocyte/erythrocyte/macrophage/megakaryocyte (GEMM) colonies and blast cell colonies. Delayed addition of IL-6 or TPA decreased colony numbers, suggesting that both IL-6 and TPA were needed from the start of cultures for maximal colony formation. When cultures were started with TPA, and IL-6 was added on Day 2 of culture or later, few colonies developed. These data suggested that IL-6 might be essential to the survival of the progenitors in culture. Chronic exposure of progenitors to TPA prior to the culture with IL-6+TPA suppressed colony formation. Addition of calphostin C, a specific protein kinase C (PKC) inhibitor or genistein and herbimycin A, specific tyrosine kinase (TK) inhibitors to the culture also decreased colony numbers formed with IL-6 and TPA. To clarify which effects of IL-6 or TPA on colony formation were blocked by the inhibitors, the inhibitors were added to preincubation of progenitors with IL-6. Both the PKC inhibitor and TK inhibitors blocked the increase of colonies resulted from a pre-incubation with IL-6. Although delayed addition of TPA enhanced IL-6-dependent colony formation, delayed addition of TPA with either the PKC inhibitor or TK inhibitors canceled the increase of colonies. These data suggested that both signals of IL-6 and TPA might be transduced via activation of PKC and TK, but further studies are needed to confirm that.
 ...
PMID:[Colony formation of mouse primitive hemopoietic progenitors with interleukin-6 and phorbol ester, and their signal transduction]. 786 57

We have recently demonstrated a large induction of keratinocyte growth factor expression in dermal fibroblasts during wound healing. To identify possible mediators of KGF induction, we have now analysed the regulation of KGF expression in vitro in cultured murine and human fibroblasts. Here we demonstrate that KGF mRNA and protein expression is low in quiescent fibroblasts but is strongly induced upon serum stimulation. This induction can be mediated by at least two different intracellular pathways involving protein kinase C or cAMP-dependent kinases. Our finding that induction of KGF expression by serum is independent of de novo protein synthesis demonstrates, that KGF is the product of a primary response gene. The stimulatory effect of serum on KGF expression is likely to be a combinatorial effect of different mitogens, since several purified serum growth factors also stimulated KGF expression but to a lesser extent compared to serum. Furthermore, we also found a strong KGF induction by interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6, cytokines which are released by polymorphonuclear leukocytes and activated macrophages during wound healing. These data suggest that serum which is released upon hemorrhage as well as pro-inflammatory cytokines might be responsible for the KGF induction in vivo during skin repair.
 ...
PMID:Large induction of keratinocyte growth factor expression by serum growth factors and pro-inflammatory cytokines in cultured fibroblasts. 793 42

The mechanism of protein kinase C (PKC) induced release of the soluble interleukin-6 receptor (sIL-6R) from human B cells was investigated. Phorbol myristat acetat (PMA)-induced activation of PKC significantly enhanced the release of sIL-6R from the human B-cell line SKW 6.4. The PMA effect was completely blocked by cycloheximide, whereas different inhibitors of proteases had no effect. In contrast to the effect on sIL-6R release, FACS analysis did not reveal any effect of PMA on the expression of IL-6R on the surface of SKW 6.4 cells. After 6 h of stimulation with PMA, analysis of mRNA expression using a polymerase chain reaction-(PCR)-assisted mRNA amplification assay, showed increased expression of a spliced mRNA encoding for a soluble form of IL-6R. Comparable to the results in SKW 6.4 cells, activation of purified human B cells with PMA induced a significant augmentation of sIL-6R release which was also sensitive to cycloheximide. In conclusion, a novel mechanism of sIL-6R release is reported involving de novo synthesis. Thus, sIL-6R release from human B cells is completely different compared with that described in hepatocytes, which involved rapid, proteolytic cleavage of the membrane-bound receptor but not de novo synthesis. The results of this study may help to understand the molecular control of sIL-6R release from human B cells.
 ...
PMID:Activation of protein kinase C induces de novo synthesis of the soluble interleukin-6 receptor in human B cells. 797 58

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

We have reported recently that colchicine and other microtubule-disrupting agents stimulated interleukin-1 (IL-1) alpha and beta synthesis in human monocytes. In this study we found that unexpectedly colchicine failed to stimulate the expression of two other potent immune mediators, namely tumor necrosis factor-alpha and interleukin-6. Remarkably, taxol which induces stable microtubule bundles, antagonized the colchicine but not the LPS-induced IL-1 synthesis. These results suggested that the colchicine-mediated IL-1 induction was generated by microtubule disassembly. We next demonstrated that microtubule disruption triggered an elevation of intracellular levels of cAMP and a subsequent stimulation of protein kinase A. The use of different protein kinase inhibitors supported a role of the PKA, but not the PKC, in the colchicine-induced IL-1 production. Furthermore, elevation of intracellular cAMP levels by 8-bromo-cAMP, forskolin, or cholera toxin potentiated the effect of suboptimal concentration of colchicine on IL-1 synthesis. However, these agents alone were unable to induce IL-1 synthesis. Therefore, our data indicate that the cAMP/protein kinase A-signaling pathway is necessary but not sufficient to generate IL-1 synthesis by microtubule disruption. Thus, microtubule-disrupting drugs appear as useful tools to further characterize the molecular events which regulate IL-1 production in human monocytes.
 ...
PMID:Disruption of microtubule network in human monocytes induces expression of interleukin-1 but not that of interleukin-6 nor tumor necrosis factor-alpha. Involvement of protein kinase A stimulation. 809 11

Interleukin-1 beta depresses the voltage-gated Ca2+ channel currents in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with pathophysiological concentrations found in the cerebrospinal fluid (> or = 1.0 pg interluekin-1 beta/10 microliters). Interleukin-1 receptor antagonist (in concentrations 25-fold higher than interleukin-1 beta) completely blocked the interleukin-1 beta-induced depression of the Ca2+ channel current. This suggests that interleukin-1 beta action is through a specific interaction with an interleukin-1 membrane receptor site. The application of other cytokines and growth factors (interleukin-6, epidermal growth factor, and basic fibroblast growth factor), or bacterial lipopolysaccharide (endotoxin) had no effect, indicating specificity of action of interleukin-1 beta. The depression of the Ca2+ channel current by interleukin-1 beta was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[beta S], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12-myristate 13-acetate also depressed the Ca2+ channel current, but this phorbol ester-induced depression was not additive to that induced by interleukin-1 beta. These results suggest mediation of interleukin-1 beta action through a pertussis toxin-sensitive G-protein coupled interleukin-1 receptor associated with the activation of protein kinase C. The depression of the Ca2+ channel current by interleukin-1 beta may be involved in the regulation of neuronal excitability during pathological conditions and in the induction and/or progression of neurodegenerative processes.
 ...
PMID:Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. 813 77

One of the members of the bZIP family of transcriptional activators is NF-IL6/LAP (IL-6 DBP, C/EBP beta, CRP2). NF-IL6/LAP protein is highly expressed in liver nuclei, where it has been implicated as a master regulator of the acute-phase response, induced by interleukin-6 (IL-6) and other inflammatory mediators. Also, NF-IL6/LAP is involved in the activation of the IL-6 promoter in response to IL-1 and bacterial lipopolysaccharide. The control of NF-IL6/LAP expression and activity is complex and poorly understood. Under some conditions the NF-IL6/LAP gene is transcriptionally activated by IL-1 and lipopolysaccharide, whereas in other instances, its binding to cognate DNA sequences is enhanced by cytokines. Additionally, the ability of constitutively expressed NF-IL6/LAP to activate transcription is strongly augmented by IL-6, through an unknown signalling pathway. We now show that stimulation of the protein kinase C pathway increases the phosphorylation of Ser 105 within the activation domain of NF-IL6/LAP, and enhances its transcriptional efficacy.
 ...
PMID:Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain. 833 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>