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

Interleukin-1 (IL-1), a cytokine involved in the acute phase reaction to injury and infection, has multiple effects in the central nervous system, including induction of fever and sleep and the release of several neuropeptides. We evaluated effects of IL-1 beta on inhibitory postsynaptic function at the gamma-aminobutyric acidA (GABAA) receptor. IL-1 (100 pg/ml to 10 ng/ml) augmented GABAA receptor function in cortical synaptic preparations. This effect of IL-1 was largely prevented by incubation with a specific IL-1 receptor antagonist. The related cytokines interleukin-6 and tumor necrosis factor did not augment GABA-dependent chloride transport. Similar enhancement of GABAA receptor function was observed in tissue prepared from mice previously injected intraperitoneally with IL-1 (1 microgram). Electrophysiological studies in cultured primary cortical neurons demonstrated that IL-1 enhanced the GABA-mediated increase in chloride permeability, whereas IL-1 alone produced no alterations in resting conductance. Behavioral studies indicated that IL-1 is similarly active in vivo; mice treated with IL-1 showed a decrease in open-field activity and an increase in the threshold for pentylenetetrazol-induced seizures. The interaction of IL-1 with GABAA receptors might account for the somnogenic and motor-depressant effects of this cytokine.
Mol Pharmacol 1991 Feb
PMID:Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain. 184 88

The data are presented on the cloning and sequencing of cDNA coding for human interleukin-6. The variability of cDNA proIL-6 cloned from different cellular sources was studied. The variability of cDNA proIL-6 may be expressed as heterogeneity of 5'- and 3'-end sequences of cDNA as well as single base-pair changes.
Mol Gen Mikrobiol Virusol 1991 May
PMID:[Molecular cloning of cDNA encoding human prointerleukin-6]. 189 55

Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines, recently have been identified as physiological inducers of hematopoietic cell differentiation which also induce terminal differentiation and growth arrest of the myeloblastic leukemic M1 cell line. In this work, it is shown that c-myc exhibited a unique pattern of expression upon induction of M1 terminal differentiation by LIF or IL-6, with an early transient increase followed by a decrease to control levels by 12 h and no detectable c-myc mRNA by 1 day; in contrast, c-myb expression was rapidly suppressed, with no detectable c-myb mRNA by 12 h. Vectors containing the c-myc gene under control of the beta-actin gene promoter were transfected into M1 cells to obtain M1myc cell lines which constitutively synthesized c-myc. Deregulated and continued expression of c-myc blocked terminal differentiation induced by IL-6 or LIF at an intermediate stage in the progression from immature blasts to mature macrophages, precisely at the point in time when c-myc is normally suppressed, leading to intermediate-stage myeloid cells which continued to proliferate in the absence of c-myb expression.
Mol Cell Biol 1991 May
PMID:Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc. 190 40

Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), two multifunctional cytokines lacking structural homology and binding to distinct receptors, share interesting functional similarities, which include induction of hematopoietic differentiation in normal and myeloid leukemia cells, induction of neuronal cell differentiation, and stimulation of acute-phase protein synthesis in hepatocytes. Structural information on the LIF receptor is not yet available, whereas recent cloning of the IL-6 receptor has shown it to be bipartite, with a signal-transducing subunit that lacks sequence homology to known protein kinases and produces second messengers of unknown nature. The molecular nature of the mechanisms which LIF and IL-6 use to induce cell differentiation is not known. To address this issue, we took advantage of a clone of M1 myeloblastic leukemia cells capable of being induced for terminal differentiation by both LIF and IL-6 directly activate the same set of immediate early response genes upon induction of M1 myeloid differentiation. At least two mechanisms of gene activation, one transcriptional and the other posttranscriptional, are shown to be involved. It is also shown that the LIF and IL-6 immediate early response, at suboptimal cytokine concentrations, is additive. Using a variety of protein kinase activators and inhibitors, we have shown that the intracellular signalling pathways for both LIF and IL-6 are distinct from those of known second messengers and involve protein phosphorylation, notably tyrosine phosphorylation of a 160-kDa protein, as an essential step(s) in the immediate early activation of MyD gene expression. These observations indicate that the functional similarities of LIF and IL-6 as inducers of cell differentiation prevail at the level of the complex differentiation immediate early response and implicate common mechanisms of signal transduction for LIF- and IL-6-induced differentiation.
Mol Cell Biol 1991 Sep
PMID:Leukemia inhibitory factor and interleukin-6 trigger the same immediate early response, including tyrosine phosphorylation, upon induction of myeloid leukemia differentiation. 190 51

Epithelial cells are likely to modulate inflammation and tissue repair in the airways, but the factors responsible for these processes remain unclear. Because human airway epithelia are infrequently available for in vitro studies, transformed epithelial cell lines are of interest as models. We therefore investigated the response of an SV-40/adenovirus-transformed human bronchial epithelial cell line (BEAS-2B) to histamine, a mediator with relevance for airway diseases. The intracellular calcium response to histamine (10(-4) M) was measured, using Fura-2 and microspectrofluorimetry. Histamine induced a transient increase in intracellular calcium that originated from intracellular sources; this effect was inhibited by the H1 receptor antagonist diphenhydramine, suggesting that BEAS cells retain functioning histamine receptors. BEAS cells were grown to confluence on microporous, collagen-coated filters, allowing measurement of vectorial release of soluble mediators. Monolayers exposed to histamine for 30 min released interleukin-6 and fibronectin in the apical direction, in a dose-dependent manner. Little eicosanoid production was induced by histamine, either in the apical or the basolateral direction, although BEAS cells constitutively produced small amounts of prostaglandin E2 and 15-HETE. However, these cells formed large amounts of eicosanoids in response to ozone exposure as a positive control. Comparison of our data with published reports for human airway epithelia in primary culture suggests that the BEAS cell line is, in a number of respects, a relevant model for the study of airway epithelial responses to a variety of stimuli.
Am J Respir Cell Mol Biol 1991 Nov
PMID:The response of a human bronchial epithelial cell line to histamine: intracellular calcium changes and extracellular release of inflammatory mediators. 193 Oct 77

Recent studies have suggested that intestinal epithelial cells demonstrate some of the functions associated with immune competent cells. Based on these observations, we investigated whether gastrointestinal epithelial cells express Interleukin-6 (IL-6). The presence of this cytokine was tested in 53 normal and pathological tissue specimens of the human gastrointestinal tract using an immunohistochemical technique with anti-IL-6 monoclonal and polyclonal antibodies. Immunostaining shows that IL-6 is expressed in gastric and small intestinal epithelial cells. The tumor cells from a large subset (11 of 15) of colon cancer specimens were strongly immunostained. IL-6 immunostaining was less conspicuous and less frequent in the epithelial cells of normal colonic mucosa. Northern blot experiments indicated that the expression of IL-6 in colonic mucosa correlates quantitatively with the presence of its m-RNA. Furthermore, IL-6 receptor (IL-6R) m-RNA was also detected and was twice as abundant in colonic carcinoma as in normal colon. It is concluded that mucosal epithelial cells of the gastrointestinal system express IL-6 and that in the case of the colon, malignancy is accompanied by a higher expression. In addition, the presence of IL-6R transcript suggests that normal and neoplastic colonic epithelial cells might be autocrinally regulated by IL-6.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Interleukin-6 and its receptor are expressed in human intestinal epithelial cells. 197 Jun 94

During the acute phase response to bacterial endotoxin in rats, hepatic levels of cytochrome P450IIC12 [AH, reduced flavoprotein:oxygen oxidoreductase (RH hydroxylating), EC 1.14.14.1] (P450IIC12) apoenzyme and mRNA are suppressed. We set out to determine the effects of potential humoral mediators of inflammation on the expression of P450IIC12 in female rats. A single injection of 12,000 or 60,000 units of interleukin-1 alpha had no effect on total cytochrome P450 content or P450IIC12 mRNA measured 12 hr later, although P450IIC12 apoenzyme was slightly but significantly increased by the higher dose. In the second experiment, animals were given dexamethasone (100 micrograms/kg at -30 min), interleukin-1 alpha (30,000 units/kg at 0, 2, and 4 hr), or both and were sacrificed at 12 hr. Treatment with interleukin-1 alpha alone significantly suppressed total cytochrome P450, P450IIC12 apoenzyme, and P450IIC12 mRNA to 77, 53, and 65% of control levels, respectively; beta-actin mRNA was significantly increased (206% of control levels). Treatment with dexamethasone alone suppressed total cytochrome P450 and P450IIC12 mRNA (73% of controls) but did not significantly affect P450IIC12 apoenzyme measured 12.5 hr later. Again, beta-actin mRNA was increased. When both interleukin-1 alpha and dexamethasone were given, total cytochrome P450 and P450IIC12 mRNA (43% of controls) were suppressed, and beta-actin mRNA was significantly increased. In the third experiment, animals were injected at 0 and 12 hr with dexamethasone (83 micrograms/kg), interleukin-6 (33 micrograms/kg), or both. Interleukin-6 alone did not significantly affect total cytochrome P450 or P450IIC12 apoenzyme or mRNA. Dexamethasone alone suppressed P450IIC12 apoenzyme and mRNA (to 52 and 41%, respectively, of controls). Treatment with both interleukin-6 and dexamethasone significantly suppressed total cytochrome P450 and P450IIC12 apoenzyme and mRNA; suppression of P450IIC12 mRNA (to 16% of controls) was greater than with dexamethasone alone. No change in the transcription rate of CYP2C12 was observed 24 hr after initiation of treatment with dexamethasone (83 micrograms/kg at 0 and 12 hr) or 12 hr after initiation of treatment with interleukin-1 alpha (30,000 units/kg at 0, 2, and 4 hr). We conclude that, in this model, interleukin-1 alpha and glucocorticoids are important mediators of the suppression of hepatic P450IIC12 expression during inflammation. Interleukin-6 was not as potent, but it did potentiate the effects of dexamethasone. Suppression of P450IIC12 expression by dexamethasone and interleukin-1 alpha appeared to be mediated at a pretranslational level, but the possibility of a transcriptional effect needs to be further investigated.
Mol Pharmacol 1991 Apr
PMID:Regulation of cytochrome P450IIC12 expression by interleukin-1 alpha, interleukin-6, and dexamethasone. 201 47

The interleukin-6 (IL-6) promoter is rapidly and transiently activated with other cytokines, including IL-1, tumor necrosis factor, and platelet-derived growth factor, as well as phorbol esters and agents that increase intracellular cyclic AMP. In this study, we have investigated cis-acting regulatory elements and trans-acting factors responsible for IL-1-induced IL-6 gene expression. Studies on the 5' deletion mutants of the human IL-6 gene suggested that the IL-1-responsive element was mapped within the IL-6 promoter region (-180 to -123) which was homologous to the c-fos serum-responsive enhancer element. Gel retardation assay identified two types of nuclear factors that bound to this region, one constitutive and the other inducible. These two factors recognized a 14-base-pair (bp) palindromic sequence, ACATTGCACAATCT. Furthermore, three copies of this 14-bp palindrome conferred IL-1 responsiveness to the basal enhancerless IL-6 promoter, indicating that a 14-bp-dyad symmetry sequence was an IL-1-responsive element in the IL-6 gene.
Mol Cell Biol 1990 Jun
PMID:Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene. 211 42

We have investigated the role that hemopoietic regulatory molecules may play in mouse embryogenesis prior to the appearance of hemopoietic stem cells or their microenvironments. Using polymerase chain reaction analysis, we detected mRNA transcripts for interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) but not for granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3 in mouse blastocysts at 3.5 days of gestation. Functional IL-6 protein was also detected in cultured blastocysts as a secreted product, as was an activity consistent with the presence of LIF protein. The expression of IL-6 and LIF in blastocysts prior to hemopoiesis suggests that these proteins may regulate the growth and development of trophoblasts or embryonic stem cells.
Mol Cell Biol 1990 Sep
PMID:The genes for leukemia inhibitory factor and interleukin-6 are expressed in mouse blastocysts prior to the onset of hemopoiesis. 211 4

IL6-PE40 is a chimeric toxin composed of human interleukin-6 (IL6) linked by a peptide bond to PE40, a form of Pseudomonas exotoxin (PE) devoid of its cell recognition domain. To identify cancer cell lines with high numbers of IL6 receptors and to assess the usefulness of IL6-PE40 as a possible anticancer agent, we evaluated the toxicity of IL6-PE40 on a variety of tumor cell lines and demonstrated that certain human myeloma and hepatoma cell lines were particularly sensitive. IL6 binding to selected hepatoma and myeloma cell lines were determined by using [125I]IL6. IL6 receptor mRNA levels were measured by polymerase chain reactions. When comparisons were made among different hepatoma cell lines, the sensitivity to IL6-PE40 correlated with the number of IL6 receptors. However, the hepatoma line PLC/PRF/5, which contains 2,300 IL6 receptors, was more sensitive to IL6-PE40 (amount of protein required to inhibit protein synthesis by 50% was 5 ng/ml) than both the myeloma cell lines U266 and H929 (for both cell lines, the 50% inhibitory dose was 8 ng/ml), which contain 15,500 and 16,500 IL6 receptors, respectively. RNA analysis confirmed that the sensitivity of these cells to IL6-PE40 and the amount of IL6 receptor RNA detected did not correlate. These data suggest that factors in addition to the number of IL6-binding sites contribute to the sensitivity of cells to IL6-PE40.
Mol Cell Biol 1990 Jun
PMID:Cell-specific toxicity of a chimeric protein composed of interleukin-6 and Pseudomonas exotoxin (IL6-PE40) on tumor cells. 216 May 79


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