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

The cross-linkage of high affinity Fc epsilon receptors (Fc epsilon RI) on mast cells and basophils is central to the induction of allergic inflammatory responses. As a result of such cross-linkage, mast cells secrete a variety of preformed biologically active substances, such as histamine, and newly synthesized arachidonic acid metabolites. Here we show that cross-linkage of Fc epsilon RI on a series of nontransformed murine mast cell lines, or treatment of these cells with calcium ionophores, stimulates increased messenger RNA levels and secretion of a group of lymphokines classically produced by a subset of murine T cell lines (TH2 cells). These factors include interleukin-3 (a mast cell growth factor)s interleukin-4 (an IgE 'switch factor'), interleukin-5 (an eosinophil differentiation factor) and interleukin-6 (a factor controlling immunoglobulin secretion). The production of these polypeptide factors by mast cells may have great importance in the induction of allergic and anti-parasite inflammatory responses.
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PMID:Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. 246 65

Two cDNA clones encoding a receptor for human granulocyte-macrophage colony-stimulating factor (hGM-CSF-R) were isolated by expression screening of a library made from human placental mRNA. Pools of recombinant plasmid DNA were electroporated into COS cells which were then screened for their capacity to bind radioiodinated hGM-CSF using a sensitive microscopic autoradiographic approach. The cloned GM-CSF-R precursor is a 400 amino acid polypeptide (Mr 45,000) with a single transmembrane domain, a glycosylated extracellular domain and a short (54 amino acids) intracytoplasmic tail. It does not contain a tyrosine kinase domain nor show homology with members of the immunoglobulin super gene family, but does show some significant sequence homologies with receptors for several other haemopoietic growth factors, including those for interleukin-6, erythropoietin and interleukin-2 (beta-chain) and also to the prolactin receptor. When transfected into COS cells the cloned cDNA directed the expression of a GM-CSF-R showing a single class of affinity (KD = 2(-8) nM) and specificity for human GM-CSF but not interleukin-3. Messenger RNA coding for this receptor was detected in a variety of haemopoietic cells known to display hGM-CSF binding, and cross-linking experiments revealed a similar size for the glycosylated receptors in transfected COS and haemopoietic cells.
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PMID:Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. 255 71

Recombinant human interleukin-6 produced a dose-dependent inhibition of DNA synthesis in both growing and mitogen-stimulated cultures of normal rat liver epithelial cells and also in primary rat hepatocytes. A significant inhibition of DNA synthesis (P less than 0.001) was obtained with 1 ng/ml (10 Units/ml) interleukin-6 in normal rat liver epithelial cells. The ID50 for inhibition of DNA synthesis in primary rat hepatocytes was 1 ng/ml. In contrast to the effects of transforming growth factor beta (Type I), where an almost complete inhibition of DNA synthesis could be achieved with either cell type, the maximal inhibition observed with interleukin-6 for both of these cell types was about 45%. Thus distinct mechanisms are involved in the inhibition of liver cell growth by these growth modulators. Transformed liver-derived cell lines were relatively resistant to the growth inhibitory effects of both interleukin-6 and TGF-beta 1 compared with the normal cells. However, human Hep G2 cells, which were completely resistant to the growth inhibitory effects of TGF-beta 1, were moderately inhibited by interleukin-6, indicating that the mechanisms responsible for the acquired resistance to growth inhibition is different for these growth inhibitors. The ability of interleukin-6 to function as a growth inhibitor in vitro was confirmed using normal rat liver epithelial cells. Interleukin-6 at a concentration of 10 ng/ml produced a significant decrease (P less than 0.05) in the proliferation of these cells. These data demonstrate that interleukin-6 may have the capability of functioning as a growth regulatory polypeptide for liver cells in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of interleukin-6 on the growth of normal and transformed rat liver cells in culture. 263 56

The recR gene of Escherichia coli, which is associated with recBC-independent mechanisms of recombination and DNA repair, has been located between dnaZX and htpG on a 6.4 kb EcoRI fragment of DNA that has been cloned and analysed in lambda and plasmid vectors. Nucleotide sequencing of this interval revealed two open reading frames that constitute an operon lying immediately downstream of dnaZX. The second of these two reading frames was identified as recR. It encodes a polypeptide with a predicted molecular weight of 21,965 Daltons that migrates on SDS gels as a 26 kDa protein. The first gene of the operon encodes a polypeptide of 12,015 daltons. Its function is not known.
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PMID:The recR locus of Escherichia coli K-12: molecular cloning, DNA sequencing and identification of the gene product. 267 3

Interleukin-6 mediates pleiotropic functions in various types of cells through its specific receptor (IL-6-R), the cDNA of which has already been cloned. We report here that an 80 kd single polypeptide chain (IL-6-R) is involved in IL-6 binding and that IL-6 triggers the association of this receptor with a non-ligand-binding membrane glycoprotein, gp130. The association takes place at 37 degrees C within 5 min and is stable for at least 40 min in the presence of IL-6, but does not occur at 0 degree C. Human IL-6-R can associate with a murine gp130 homolog and is functional in murine cells. Mutant IL-6-R lacking the intracytoplasmic portion is functional, suggesting that the two polypeptide chains interact to involve their extracellular portion. In fact, a soluble IL-6-R lacking the transmembrane and intracytoplasmic domains can associate with gp130 in the presence of IL-6 and mediate its function. These findings indicate that the complex of IL-6 and IL-6-R can interact with a non-ligand-binding membrane glycoprotein, gp130, extracellularly and can provide the IL-6 signal.
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PMID:Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. 278 34

Astrocytes have a critical role in the neuronal response to ischemia, as their production of neurotrophic mediators can favorably impact on the extreme sensitivity of nervous tissue to oxygen deprivation. Using a differential display method, a novel putative RNA binding protein, RA301, was cloned from reoxygenated astrocytes. Analysis of the deduced amino acid sequence showed two ribonucleoprotein domains and serine/arginine-rich domains, suggestive of their function as RNA splicing factor. Northern analysis displayed striking induction only in cultured astrocytes within 15 min of reoxygenation and reached a maximum by 60 min after hypoxia/reoxygenation. Immunoblotting demonstrated expression of an immunoreactive polypeptide of the expected molecular mass, 36 kDa, in lysates of hypoxia/reoxygenated astrocytes. Induction of RA301 mRNA was mediated, in large part, by endogenously generated reactive oxygen species, as shown by diphenyl iodonium, an inhibitor of neutrophil-type nicotinamide adenine dinucleotide phosphate oxidase which blocks oxygen-free radical formation by astrocytes. Similarly, increased expression of RA301 in supporting a neurotrophic function of astrocytes was suggested by inhibition of interleukin-6 elaboration, a neuroprotective cytokine, in the presence of antisense oligonucleotide for RA301. These studies provide a first step in characterizing a novel putative RNA binding protein, whose expression is induced by oxygen-free radicals generated during hypoxia/reoxygenation, and which may have an important role in redirection of biosynthetic events observed in the ischemic tissues.
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PMID:Cloning of a novel RNA binding polypeptide (RA301) induced by hypoxia/reoxygenation. 749 16

The human glycoprotein hormone alpha-gene is transcriptionally activated by cAMP in placental cells. We have shown that the novel hypothalamic peptide, pituitary adenylate cyclase activating polypeptide, PACAP-38, significantly stimulates intracellular cAMP levels (12-fold increase; P < 0.001) in JEG-3 choriocarcinoma cells. Regulation of alpha-promoter activity was assessed using both the chloramphenicol acetyl transferase (CAT) and the luciferase (LUC) reporter gene systems. alpha-CAT activity was significantly stimulated by PACAP-38 (4-fold increase; P < 0.05) at 24 h with a similar stimulation being seen with a LUC expression vector. The kinetics of stimulation of the alpha-promoter by PACAP-38 were similar to those seen with 8-Br-cAMP and vasoactive intestinal polypeptide (VIP), a peptide which shares 68% homology with PACAP-38. PACAP-38 also stimulated the production of IL-6 from JEG-3 cells with a time course of response similar to that of alpha-promoter transcription. We conclude that human placental choriocarcinoma cells possess functional receptors for PACAP-38, whose activation enhances cAMP formation, alpha-subunit gene transcription and interleukin-6 (IL-6) production.
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PMID:PACAP-38 positively regulates glycoprotein hormone alpha-gene expression in placental cells. 751 49

Here we report that soluble CD14 isolated from the urine of nephrotic patients (uCD14) contains a potent cytokine inducing activity. CD14 derived from urine appeared to consist of two major polypeptides of about 54 and 48 kDa. In uCD14 isolated from three different nephrotic patients the cytokine-inducing activity appeared to co-migrate with the 48-kDa polypeptide which upon sequencing had the same N-terminal sequence as native CD14. Treatment of human monocytes and the human astrocytoma cell line U373 with uCD14 resulted in a strong secretion of tumor necrosis factor (TNF) and interleukin-6, respectively. The cytokine-inducing activity of the uCD14 preparations was unaffected by the absence of serum. This is in contrast to the activation of human monocytes and U373 cells by lipopolysaccharide (LPS) which is highly dependent on the presence of serum. The cytokine-inducing activity was not affected by LPS-binding protein (LBP) or polyclonal rabbit antibodies against LBP. The TNF-inducing activity of uCD14 was also heat labile in contrast to the cytokine-inducing activity of LPS, which was relatively heat resistant. The results suggest that CD14 may exist in at least two forms of which one is involved in cytokine induction.
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PMID:Soluble CD14 from urine copurifies with a potent inducer of cytokines. 751 94

Platelet-derived growth factor (PDGF) increases bone resorption and the number of osteoclasts in calvarial sections, and it may regulate local cytokines involved in bone remodeling. Interleukin-6 (IL-6), a cytokine secreted by osteoblasts, osteoclasts, and stromal cells, is known to increase osteoclast recruitment. We tested the effects of PDGF on IL-6 expression in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). Treatment of Ob cells with PDGF BB caused a time- and dose-dependent induction of IL-6 messenger RNA (mRNA), as determined by Northern blot analysis. The effect was maximal after 1 h of treatment and was observed with PDGF BB at 0.3-3.3 nM. Treatment with PDGF BB for 24 h also increased IL-6 polypeptide levels in the culture medium, as determined by a specific bioassay. Although PDGF AA increased IL-6 mRNA levels, its effect was less pronounced than that of PDGF BB. Phorbol 12-myristate 13-acetate (PMA) induced IL-6 transcripts, and the effect of PDGF BB was inhibited in the presence of the protein kinase C (PKC) inhibitor, sangivamycin, or after down-regulation of PKC by PMA preincubation. Although forskolin increased IL-6 mRNA levels, PDGF BB did not induce cAMP production in Ob cells. The calcium ionophore, ionomycin, enhanced IL-6 transcripts in Ob cells and the intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester, inhibited the induction of IL-6 transcripts by PDGF BB, PMA, and PTH. In conclusion, PDGF BB stimulates IL-6 expression in Ob cells, a response that is PKC and calcium dependent. The increase in IL-6 expression may be relevant to the actions of PDGF BB on bone resorption.
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PMID:Platelet-derived growth factor stimulates the synthesis of interleukin-6 in cells of the osteoblast lineage. 758 97

A major challenge in basic and applied biological research is the engineering of small proteins with pre-determined structures and novel functions. In a limited number of cases, this has been achieved by de novo design. An alternative combinatorial approach is based on the construction of large libraries of random peptides and on methods for the selection of the desired molecules. Here we describe a successful combination of both the rational design and the combinatorial approaches for developing proteins with useful biological functions, in this case the construction of a specific inhibitor of the cytokine human interleukin-6. In previous work, the 'minibody', a 61 residue polypeptide consisting of a beta-pleated framework and two hypervariable regions, was designed, synthesized and expressed on f1 phage surface. We report the construction of a repertoire of 50 million minibodies displayed on phage in which the hypervariable regions have been randomized. One polypeptide which binds tightly and specifically to human interleukin-6 was isolated from this collection of minibody mutants. This particular minibody is an effective inhibitor of the cytokine's biological activity. The approach described here could in principle be applied to other molecular targets.
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PMID:The affinity-selection of a minibody polypeptide inhibitor of human interleukin-6. 795 96


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