UNIPROT:P05231 - FACTA Search

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

Endothelins (ET) are vasoactive polypeptide hormones that stimulate osteoblastic signal transduction events. Using MC3T3-E1 and primary osteoblasts, we studied ET effects on interleukin-6 (IL-6) and macrophage colony-stimulating factor (M-CSF) production. Enzyme-linked immunosorbent assay analysis showed a dose-dependent 3- to 3.5-fold increase in IL-6 with 100 nM ET-1 stimulation within 4 (primary osteoblasts) to 8 (MC3T3-E1) h. ET-3 was less effective at enhancing IL-6 production, with a maximal twofold increase after 100 nM ET-3 after 4 h. No significant increase in M-CSF production was noted with ET-1 or ET-3 in either cell type. Reverse-transcriptase polymerase chain reaction analysis demonstrated both ET(A) and ET(B) receptors on primary osteoblasts and only ET(A) receptors on MC3T3-E1. ET-1-stimulated IL-6 production was blocked by the inhibitor BQ-123, implicating ET(A) receptor involvement. Increased IL-6 protein was coupled with elevated IL-6 mRNA levels and a twofold increase in IL-6 message half-life.
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PMID:Endothelin stimulates osteoblastic production of IL-6 but not macrophage colony-stimulating factor. 912 53

Pituitary adenylate cyclase activating polypeptide was first isolated from sheep hypothalamus by its potent activity in stimulating cyclic adenosine monophosphate production in anterior pituitary cells. The present review deals with the actions of this polypeptide on anterior pituitary cell types and with the putative role of the polypeptide as a hypophysiotropic factor regulating anterior pituitary cell activity. The evidence to date is strongly suggestive that pituitary adenylate cyclase activating polypeptide may act not as a "classic" hypophysiotropic factor stimulating or modifying anterior pituitary hormone release in vivo, since it does not appear in vitro to be a particularly potent stimulator of hormone release. The polypeptide rather may modulate the responses to factors such as gonadotrop hormone releasing hormone or have more general actions by regulating hormone synthesis or cell differentiation. Pituitary adenylate cyclase activating polypeptide also has indirect actions on anterior pituitary cell activity by stimulating the release of the paracrine factor interleukin-6. Its receptors appear to be present on most of the anterior pituitary cell types and unlike many other hypophysiotropic factors, pituitary adenylate cyclase activating polypeptide interacts with most, if not all, of the anterior pituitary cell types. Its exact effects and mechanisms of action in the anterior pituitary gland are still poorly understood.
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PMID:[Effect of pituitary adenyl cyclase activating polypeptide on the cells of anterior pituitary cells]. 944 Dec 67

The body's general response to serious thermal injury is characterized by increased vascular permeability immediately after injury and subsequent hypovolemic shock. Skeleto-muscular proteolysis, lipolysis, gluconeogenesis, increased metabolic rate, and a severe systemic inflammatory response induced by local infections or surgical procedures. The increased vascular permeability is mediated by histamine and numerous vasoactive substances, including serotonin, bradykinin, prostaglandins, leukotrienes, and platelet activating factor. Hyper-metabolism is mediated by hormones such as catecholamines, glucagon, and particularly cortisol. In addition, among the putative mediators of the metabolic response to injury, attention has recently been focused on cytokines and lipid mediators which are mainly produced by activated reticuloendothelial cells. Cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor and cortisol responses are interrelated, since cytokines activate the hypothalamo-adrenal axis. The cytokine storm seen in burn patients may be associated with depression of the immune system and with susceptibility to infection. Thermal injury can also lead to activation of the renin-angiotensin-aldosterone system, increased ADH production, and production of atrial natriuretic polypeptide to maintain the circulatory volume. Burn wound infections or surgical procedures can produce and perpetuate a mediator-induced systemic inflammatory response that may lead to multiple organ failure. Serum levels of interleukin-6 are very sensitive to surgical stress, and may be a useful indicator of the general condition of severely burned patients.
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PMID:[Pathophysiologic changes in patients with severe burns: role of hormones and chemical mediators]. 954 40

The gp130 cytokines leukemia inhibitory factor and interleukin-6 are neuroactive cytokines associated with peripheral nerve injury. Here we show that exogenous administration of these factors selectively regulates neuropeptide phenotype in intact sensory neurons in a manner consistent with their role as injury-induced factors. Intraneural injection of leukemia inhibitory factor into the intact sciatic nerve of adult rats induces a significant increase in the percentage of neuronal profiles immunoreactive for galanin in the L4 and L5 dorsal root ganglia without altering the percentage profiles immunoreactive for vasoactive intestinal polypeptide or neuropeptide Y. Galanin-immunoreactivity was predominantly confined to those neurons which retrogradely transported and accumulated leukemia inhibitory factor. The up-regulation of galanin-immunoreactivity observed in L4 and L5 dorsal root ganglia following unilateral axotomy of the sciatic nerve was significantly reduced following continuous treatment for two weeks with a monoclonal antibody against the gp130 receptor motif. Intraneural injection of interleukin-6 into the intact sciatic nerve also significantly increased the percentage of neuronal profiles which displayed galanin-immunoreactivity but not vasoactive intestinal polypeptide or neuropeptide Y-immunoreactivity. Our results indicate that cytokines which interact with the gp130 receptor at the site of peripheral nerve injury contribute to the cell body response to axotomy. Changes in the levels of such cytokines however are insufficient to account for the complete repertoire of neuropeptide phenotypic changes associated with peripheral nerve injury.
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PMID:gp130 cytokines, leukemia inhibitory factor and interleukin-6, induce neuropeptide expression in intact adult rat sensory neurons in vivo: time-course, specificity and comparison with sciatic nerve axotomy. 957 10

A gene, blmA, encodes a bleomycin (Bm)-binding protein, designated BLMA, from Bm-producing Streptomyces verticillus and confers resistance to Bm in Streptomyces and Escherichia coli cells. In the present study, by transfection of the gene into COS-1 cells with a plasmid designated pEF-BOS/blmA, which contains a strong promoter from the human polypeptide chain elongation factor 1alpha, we transiently overproduced BLMA at a high level of approximately 4% of the whole cell protein. Although NIH/3T3 cells transfected with pEF-BOS/blmA, designated NIH/3T3-BR cells, stably expressed BLMA, its expression level was about 0.1% of the total protein. Using an anti-BLMA monoclonal antibody reported previously [Sugiyama et al. (1995) FEBS Lett. 362, 80-84], we revealed that BLMA is localized in the nucleus of pEF-BOS/blmA-transfected COS-1 and NIH/3T3-BR cells. Semi-permeabilized nuclear transport experiments showed that BLMA penetrates the nuclear envelope by energy- and transporter-independent passive diffusion, suggesting that the karyophilic nature of BLMA may be due to the acidic nature of the protein. NIH/3T3-BR cells were 130-fold more resistant to Bm than the host cells. NIH/3T3 cells exhibited a swollen nuclear envelope and a malformed spindle body and overexpressed at least 4 kinds of stress proteins including calreticulin and mitochondrial matrix protein P1 when exposed to 25 microg/ml of Bm, whereas NIH/3T3-BR cells grew without morphological alteration and expressed no stress proteins under the same conditions. Furthermore, reverse transcription-polymerase chain reaction and Northern blot analysis showed that the expression of interleukin-6, an inflammatory cytokine, is activated by addition of Bm in NIH/3T3 cells, but not in the NIH/3T3-BR cells. These results suggest that BLMA contributes to protection of mammalian cells from the inflammatory effect of Bm.
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PMID:Protection of mammalian cells from the toxicity of bleomycin by expression of a bleomycin-binding protein gene from Streptomyces verticillus. 975 31

Interleukin-6 is one of the most well-characterized cytokines with pleiotropic properties. Besides its B-lymphocyte activation role in hematopoiesis, interleukin-6 plays a central role in regulation of systemic inflammation. Interleukin-6 binds to receptors on target cells (such as hepatocytes and lymphocytes), consisting of an 80 kDa binding chain and gp130, a polypeptide responsible for signal transduction. In addition to the detection of elevated amounts of interleukin-6 in the blood, gene expression (mRNA) of subunits of the interleukin-6 receptor complex have also been studied by examining the reverse transcriptase polymerase chain reaction on peripheral lymphocytes from patients with characteristic radiological symptoms suffering from Crohn's disease. Our data show significantly elevated gene expression both of the 80 kDa interleukin-6 binding chain and gp130. These results suggest that enhancement of the expression of the constituents of interleukin-6 and the interleukin-6 receptor system plays a relevant role in systemic inflammation in inflammatory bowel disease.
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PMID:Increased interleukin-6 levels, interleukin-6 receptor and gp130 expression in peripheral lymphocytes of patients with inflammatory bowel disease. 986 12

Heterotrimeric and small molecular mass guanine nucleotide binding (GTP-binding) proteins were found in neuronal and glial nuclei isolated from rat brain. Neuronal nuclei bound 0.213 +/- 0.055 pmoles of GTP/microg protein (n = 8) and glial nuclei bound 0.145 +/- 0.038 pmoles of GTP/microg protein (n = 8). The intrinsic GTPase activity of neuronal and glial nuclei was 0.0019 +/- 0.0005 pmoles GTP hydrolyzed/min/microg protein (n = 10) and 0.0022 +/- 0.0006 pmoles GTP hydrolyzed/min/microg protein (n = 10), respectively. Western blot analysis was carried out using a peptide-specific antibody that recognizes a common sequence in the alpha-subunit of the various heterotrimeric G-proteins. The antibody revealed the presence of a polypeptide of molecular mass of 40 kDa only in neuronal nuclei. Small molecular mass GTP-binding proteins were detected by incubating nitrocellulose blots with [alpha-32P]GTP. The results demonstrated the presence of 25-26 kDa GTP-binding proteins in both populations of nuclei. However, the binding of [alpha-32P]GTP to neuronal nuclei was approximately 3-fold greater than to the glial nuclei. Further analysis by two-dimensional polyacrylamide gel electrophoresis resolved the neuronal nuclei 26 kDa protein into three forms (a-c) with the most acidic form (c) being the major species. The neuronal 25 kDa protein was resolved into two forms that were present in approximately equal concentration. In glial nuclei, only the 26 kDa (c) and a small amount of the 25 kDa proteins were detected. However, both populations of nuclei contained the small molecular mass GTP-binding protein, ran. Differential association of non-ran small molecular mass GTP-binding proteins and heterotrimeric G-proteins with neuronal nuclei suggests a potential role for these guanine nucleotide binding proteins in the function of this cell type.
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PMID:Heterotrimeric and small molecular mass GTP-binding proteins of rat brain neuronal and glial nuclei. 989 Apr 36

The coexistence of pheochromocytoma and primary adrenal Cushing's syndrome of the same adrenal gland has rarely been reported. We describe here the case of a female patient presenting with mild Cushing's stigmata, hypertension and diabetes mellitus in whom we diagnosed a pheochromocytoma of the left adrenal gland with coexisting non-ACTH-dependent cortisol hypersecretion. While hormonal work-up was still in progress, the patient became pregnant and wanted to carry her pregnancy to full-term. A laparoscopic adrenalectomy in the 17th week of gestation was decided upon and the patient accordingly prepared for surgery by pre-treatment with phenoxybenzamine. Successful surgery--the first ever reported laparoscopic resection of a pheochromocytoma in pregnancy--without perioperative complications was performed under general anesthesia, with the patient receiving peri- and post-operative hydrocortisone substitution. Pathohistological examination revealed a pheochromocytoma with positive immunostaining for interleukin-6 (IL-6) and negative immunostaining for ACTH, vasoactive intestinal polypeptide (VIP) and cytochrome P450, and with no signs of malignancy. A paracrine stimulation of the ipsilateral adrenal cortex by IL-6 produced by the pheochromocytoma, leading to cortical hyperplasia and subclinical Cushing's syndrome, is suggested by the positive immunostaining for IL-6 and the MRI findings. Post-operatively, secondary adrenal insufficiency ensued, necessitating continuing hydrocortisone replacement over 12 months. Hypertension resolved after surgery, and diabetes after the uncomplicated vaginal delivery at term.
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PMID:Pheochromocytoma and sub-clinical Cushing's syndrome during pregnancy: diagnosis, medical pre-treatment and cure by laparoscopic unilateral adrenalectomy. 1047 54

Members of the STAT family of transcriptional regulators modulate the expression of a variety of gene products that promote cell proliferation, survival and transformation. Although initially identified as mediators of cytokine signaling, the STAT proteins are also activated by, and thus may contribute to the actions of, polypeptide growth factors. To define the mechanism by which these factors activate STATs, we examined the process of Stat3 activation in Balb/c-3T3 fibroblasts treated with platelet-derived growth factor (PDGF). As STATs are activated by tyrosine phosphorylation, and as PDGF receptors are ligand-activated tyrosine kinases, we considered the possibility that Stat3 interacts with and is phosphorylated by PDGF receptors. We find that Stat3 associates with PDGF beta receptors in both the presence and, surprisingly, the absence of PDGF. Moreover, Stat3 was phosphorylated on tyrosine in PDGF beta receptor immunoprecipitates of PDGF-treated but not untreated cells. Although required, receptor activation was insufficient for Stat3 activation. When added to cells in combination with a pharmacologic agent (PD180970) that specifically inhibits the activity of Src family tyrosine kinases, PDGF did not activate Stat3 as monitored by electrophoretic mobility shift assay. PD180970 did not affect MAPK activation by PDGF or the JAK-dependent activation of Stat3 by interleukin-6. The necessity of Src activity for Stat3 activation by PDGF was further evidenced by data showing the presence of Src in complexes containing both Stat3 and PDGF beta receptors in PDGF-treated cells. These results suggest a novel mechanism of STAT activation in which inactive Stat3 pre-assembles with inactive PDGF receptors, and in response to ligand binding and in a manner dependent on Src kinase activity, is rapidly phosphorylated and activated. Additional data demonstrate that Src kinase activity is also required for PDGF stimulation of DNA synthesis in density-arrested cells.
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PMID:Activation of Stat3 preassembled with platelet-derived growth factor beta receptors requires Src kinase activity. 1081 99

The use of so-called protein scaffolds has recently attracted considerable attention in biochemistry in the context of generating novel types of ligand receptors for various applications in research and medicine. This development started with the notion that immunoglobulins owe their function to the composition of a conserved framework region and a spatially well-defined antigen-binding site made of peptide segments that are hypervariable both in sequence and in conformation. After the application of antibody engineering methods along with library techniques had resulted in first successes in the selection of functional antibody fragments, several laboratories began to exploit other types of protein architectures for the construction of practically useful binding proteins. Properties like small size of the receptor protein, stability and ease of production were the focus of this work. Hence, among others, single domains of antibodies or of the immunoglobulin superfamily, protease inhibitors, helix-bundle proteins, disulphide-knotted peptides and lipocalins were investigated. Recently, the scaffold concept has even been adopted for the construction of enzymes. However, it appears that not all kinds of polypeptide fold which may appear attractive for the engineering of loop regions at a first glance will indeed permit the construction of independent ligand-binding sites with high affinities and specificities. This review will therefore concentrate on the critical description of the structural properties of experimentally tested protein scaffolds and of the novel functions that have been achieved on their basis, rather than on the methodology of how to best select a particular mutant with a certain activity. An overview will be provided about the current approaches, and some emerging trends will be identified. (c) 2000 John Wiley & Sons, Ltd. Abbreviations used: ABD albumin-binding domain of protein G APPI Alzheimer's amyloid beta-protein precursor inhibitor BBP bilin-binding protein BPTI bovine (or basic) pancreatic trypsin inhibitor BSA bovine serum albumin CBD cellulose-binding domain of cellobiohydrolase I CD circular dichroism Cdk2 human cyclin-dependent kinase 2 CDR complementarity-determining region CTLA-4 human cytotoxic T-lymphocyte associated protein-4 FN3 fibronectin type III domain GSH glutathione GST glutathione S-transferase hIL-6 human interleukin-6 HSA human serum albumin IC(50) half-maximal inhibitory concentration Ig immunoglobulin IMAC immobilized metal affinity chromatography K(D) equilibrium constant of dissociation K(i) equilibrium dissociation constant of enzyme inhibitor LACI-D1 human lipoprotein-associated coagulation inhibitor pIII gene III minor coat protein from filamentous bacteriophage f1 PCR polymerase-chain reaction PDB Protein Data Bank PSTI human pancreatic secretory trypsin inhibitor RBP retinol-binding protein SPR surface plasmon resonance TrxA E. coli thioredoxin
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PMID:Engineered protein scaffolds for molecular recognition. 1093 55

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