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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6) mRNA was studied in human adherent monocytes in response to the protein kinase C activator, oleolyl-acetylglycerol (OAG), the calcium-ionophore A23187 and the cyclic AMP elevating agents, dibutyryl c-AMP (DBcAMP), cholera toxin and isobutyl-methylxanthine (IBMX). G-CSF and IL-6 transcripts were simultaneously expressed in response to OAG, A23187, DBcAMP, IBMX and cholera toxin. However, the time course demonstrated a difference; a rapid induction by OAG and A23187 and a delayed pattern by cAMP elevating agents. In addition it appeared that the induction of CSFs by DBcAMP was independent of the adherence procedure or the presence of fetal bovine serum but could be counteracted by the simultaneous addition of H8, an inhibitor of the cAMP dependent kinases. Finally, experiments were performed to study in how far comparable mechanisms operate in other cell types. Human fetal lung fibroblasts were stimulated with A23187, DBcAMP and OAG. All these agents induced simultaneous expression of G-CSF and IL-6 mRNA and secretion of proteins, indicating that different signalling pathways exist in both cell types which regulate the expression of both genes.
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PMID:Simultaneous expression and regulation of G-CSF and IL-6 mRNA in adherent human monocytes and fibroblasts. 171 Apr 80

Interleukin-6 (IL-6) is an inflammatory cytokine that is produced by a variety of cells and tissues. We recently demonstrated that IL-6 is produced by anterior pituitary cells in response to the bacterial endotoxin lipopolysaccharide and phorbol diester in vitro. Lipopolysaccharide (0.01-100 ng/ml) increased, whereas dexamethasone (0.1-100 nM) decreased, IL-6 production by anterior pituitary cells in vitro as measured by the 7TD1 cell growth factor assay. In addition, we now report that IL-6 production by anterior pituitary cells is stimulated by agents that elevate intracellular cAMP concentrations. Exposure of anterior pituitary cells to (Bu)2cAMP (0.01-10 mM), prostaglandin E2 (1.0-1000 nM), forskolin (50-1000 nM), or cholera toxin (0.25-250 ng/ml) for 6 h resulted in concentration-related increases in the production of IL-6, which, in the cases of forskolin and cholera toxin, correlated well with increased intracellular cAMP concentrations. Vasoactive intestinal peptide (1-1000 nM), which stimulates adenylate cyclase activity in the anterior pituitary, caused a concentration-related enhancement of IL-6 production that was unaffected in the presence of 10-100 nM somatostatin. In contrast, GH-releasing factor had no effect on IL-6 production. These data suggest that anterior pituitary cells produce IL-6 in response to increased intracellular cAMP, and that the neuropeptide vasoactive intestinal peptide may act to regulate IL-6 production.
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PMID:Production of interleukin-6 by anterior pituitary cells is stimulated by increased intracellular adenosine 3',5'-monophosphate and vasoactive intestinal peptide. 216 22

To identify factors that regulate proliferin (PLF) and PLF-related protein (PRP) secretion by the mouse placenta, placental cells from day 9 of pregnancy were cultured for up to 5 days, and PLF and PRP release into the medium was assessed by RIA. Transforming growth factor-alpha, interleukin-1 alpha, and interleukin-6 did not regulate either PLF or PRP secretion. However, treatment of primary placental cell cultures with 8-bromo-cAMP, cholera toxin, or forskolin resulted in 2- to 3-fold increases in the percentages of PLF- and PRP-producing cells in the population and corresponding increases in both PLF and PRP messenger RNA and secreted protein. The increase in the number of PLF-producing cells was accompanied by an increase in the number of cells expressing both PLF and mouse placental lactogen-I. These data suggest that cAMP levels can regulate trophoblast giant cell differentiation and, consequently, the amount of PLF and PRP secretion.
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PMID:Cyclic adenosine 3',5'-monophosphate stimulation of placental proliferin and proliferin-related protein secretion. 772 Jun 52

Interleukin-6 (IL-6) secretion by cell cultures of human acoustic neuromas was examined. Secretory rates varied from 0.02 to 5.4 ng/10(5) cells per 4 days, depending on the tumor. The IL-6 immunoreactivity eluted from a Sephadex G-100 column in a major peak corresponding to an M(r) of 30,000 and a lesser peak corresponding to an M(r) of 50,000. Western blot analysis revealed three IL-6 immunoreactive bands with M(r)s corresponding to 53,000, 29,000, and 24,000. Tumor necrosis factor-alpha, interleukin-1-beta, and cholera toxin all stimulated IL-6 secretion. An antisense phosphorothioate oligonucleotide against IL-6 messenger RNA inhibited both [3H]thymidine uptake and IL-6 secretion by acoustic neuroma cells in culture. In addition, [3H]thymidine uptake was inhibited by a specific polyclonal antibody against IL-6. We conclude that human acoustic neuroma cells produce and secrete IL-6, which may act in an autocrine manner to stimulate cellular proliferation.
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PMID:Human acoustic neuromas secrete interleukin-6 in cell culture: possible autocrine regulation of cell proliferation. 780 Jan 35

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.
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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

Oral administration of cholera toxin (CT) induces a strong mucosal immune response to CT as well as having a potent adjuvant effect. Since one of the first cell types to encounter CT during cholera infection or after oral administration is the epithelial cell, we studied the effect of CT on interleukin-6 (IL-6) secretion by the rat intestinal epithelial cell line IEC-6. CT was found to rapidly enhance IL-6 secretion and IL-6 gene expression by these cells. The addition of dibutyryl cyclic AMP (cAMP) to cultures of IEC-6 cells had little effect on IL-6 secretion, yet mRNA levels were elevated, suggesting that the response may have been regulated by cAMP. Purified B subunit of CT did not significantly enhance IL-6 secretion or mRNA expression. CT and transforming growth factor beta 1 synergistically enhanced IL-6 secretion in IEC-6 cells. The addition of CT with either IL-1 beta or tumor necrosis factor alpha gave even greater synergistic enhancement of IL-6 secretion, and dibutyryl cAMP could mimic CT's synergy with IL-1 beta. These results indicate that the intestinal epithelial cell is capable of secreting high levels of IL-6 after encountering CT, especially in the presence of inflammatory cytokines. This high level of IL-6 secretion could be a very important component of the mucosal immune response to CT and may also account for a portion of the adjuvant effect of CT.
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PMID:Enhancing effect of cholera toxin on interleukin-6 secretion by IEC-6 intestinal epithelial cells: mode of action and augmenting effect of inflammatory cytokines. 840 61

Previous studies have suggested that activation of the adenylyl cyclase - cAMP system in meningiomas results in decreased mitosis. We have used meningioma cell culture to further investigate this phenomenon and to examine the potential role played by interleukin-6 (IL6). Incubation of cultured meningioma cells for 4-6 days with cholera toxin and theophylline, both of which increase intracellular cAMP levels, markedly stimulated IL6 secretion and inhibited cell growth rate. Similar effects were observed with 8-bromo-cAMP. In contrast, a neutralising polyclonal antibody against IL6 significantly stimulated meningioma proliferation and reduced the inhibitory effects of 8-bromo-cAMP. These results support the concept that IL6 acts as an autocrine / paracrine inhibitory factor for meningioma proliferation, and that the inhibition exerted by elevated intracellular cAMP levels may be at least partially mediated via increased secretion of the cytokine.
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PMID:Relationship between cAMP induced inhibition of human meningioma cell proliferation and autocrine secretion of interleukin-6. 861 89

Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are the strongest mucosal immunogens identified to date and are also good adjuvants when given orally together in combination with unrelated antigens. We used these potent immunogens to monitor local and systemic immune responses following oral immunization of BALB/c mice, and compared their action on the following: (a) immunoglobulin production rates (IgG, IgM and IgA) in mucosal inductive (Peyer's patches-PPs), effector (intestinal lamina propria-LP, respiratory tract) and systemic (spleen) sites; (b) analysis of systemic antigen-specific antibodies (IgG subclasses, IgA and IgE); (c) time monitoring of fecal anti-CT and anti-LT antibodies, and (d) in vivo relevance of interleukin-6 (IL-6) to mucosal responses. Both mucosal immunogens elicited specific antibody responses (IgA, IgG) not only in the gastrointestinal tract (PP's and intestinal LP), but also in the respiratory tract and spleens of orally immunized mice. These mucosal responses were accompained by elevated secretion of IL-6 in all investigated tissues, indicating involvement of this cytokine in B-cell maturation processes. Furthermore, oral immunization with CT and LT induced elevated serum titers of IgG1 followed by IgG2a, IgG2b, IgG3 and IgA, while high antigen-specific IgA and IgG1 responses were found in fecal extracts. These findings illustrate the action of orally administered CT and LT, respectively, on several humoral and cellular immune responses not only at the gastrointestinal tract, the application site, but also in distant mucosal effector sites such as the respiratory tract. These data suggest the potential use of these mucosal adjuvants in oral immunization strategies to improve the local immune response in remote mucosal tissues, in accordance with the concept of a common mucosa-associated immune system.
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PMID:Humoral and cellular immune responses in the murine respiratory tract following oral immunization with cholera toxin or Escherichia coli heat-labile enterotoxin. 881 27

We investigated the effect of prostaglandin E1 (PGE1) on the secretion of interleukin-6 (IL-6) in osteoblast-like MC3T3-E1 cells. PGE1, which induced cAMP accumulation, stimulated IL-6 secretion time-dependently up to 48 h. The stimulative effect of PGE1 was dose-dependent in the range between 10 nM and 10 microM. Cholera toxin, an activator of Gs, stimulated IL-6 secretion in MC3T3-E1 cells. Forskolin, which directly activates adenylate cyclase, significantly induced IL-6 secretion in a dose-dependent manner in the range between 1 and 50 microM. Dibutyryl cAMP (Bt2-cAMP) stimulated IL-6 secretion time-dependently up to 48 h. The effect of Bt2-cAMP on IL-6 secretion was dose-dependent in the range between 0.1 and 3 mM. N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulfonamide (H-89), a potent and selective inhibitor of protein kinase A, which suppressed the IL-6 secretion induced by forskolin or Bt2-cAMP, significantly inhibited the IL-6 secretion induced by PGE1. These results indicate that PGE1 stimulates IL-6 secretion via the activation of protein kinase A in osteoblast-like cells.
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PMID:Prostaglandin E1 stimulates interleukin-6 secretion via protein kinase A in osteoblast-like cells. 906 38

In previous studies, we have shown that prostaglandin F2alpha (PGF2alpha) stimulates interleukin-6 (IL-6) synthesis via activation of protein kinase C in osteoblast-like MC3T3-E1 cells, and that prostaglandin E1 (PGE1) induces the synthesis of IL-6 through protein kinase A activation. In the present study, we investigated the effect of vitamin D3 on IL-6 synthesis in MC3T3-E1 cells. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), an active form of vitamin D3, inhibited the IL-6 synthesis induced by PGF2alpha or PGE1. On the contrary, 24,25-dihydroxyvitamin D3, an inactive form of vitamin D3, had no effect. 1,25-(OH)2D3 did not affect the IL-6 synthesis stimulated by 12-O-tetradecanoyl-phorbol-13-acetate, an activator of protein kinase C. The IL-6 synthesis induced by cholera toxin or forskolin was significantly inhibited by 1,25-(OH)2D3. However, 1,25-(OH)2D3 had little effect on the IL-6 synthesis induced by dibutyryl cAMP. These results strongly suggest that 1,25-(OH)2D3, an active form of vitamin D3, inhibits IL-6 synthesis at both the protein kinase C pathway and the protein kinase A pathway in osteoblasts.
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PMID:Effect of vitamin D3 on interleukin-6 synthesis induced by prostaglandins in osteoblasts. 957 49


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