Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high-affinity receptor for interleukin-11 (IL-11) is composed of two subunits, IL-11 receptor alpha chain (IL-11R alpha) and gp130, the common subunit of the interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor, and oncostatin M receptors. The IL-11 receptor-specific alpha chain shares homologies with the alpha chain of the CNTF and IL-6 receptors. We isolated and characterized genomic DNA clones encompassing the entire coding sequence of the IL-11R alpha cDNA. The exon-intron organization of the IL-11R gene (HGMW-approved symbol IL11RA) is consistent with the predicted structure of the different domains of the IL-11R alpha protein, confirming evolutionary conservation at the level of gene organization among the hematopoietic cytokine receptor family. The IL-11R gene has been assigned to chromosome 9 band p13 by in situ hybridization using human IL-11R alpha cDNA as a probe. The fact that the ciliary neurotrophic factor (CNTFR) gene has recently been localized on this same band and the conserved genomic structure between IL-11R and CNTFR suggest that they may have evolved from a common ancestor.
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PMID:The human interleukin-11 receptor alpha gene (IL11RA): genomic organization and chromosome mapping. 878 20

Conditioned media were collected from phorbol ester-treated human macrophage-like U-937 cells and analyzed for the presence of inhibitors of endothelial cell (EC) proliferation. By a combination of ion exchange and reverse-phase liquid chromatography, three inhibitors were purified to homogeneity as ascertained by microsequencing of 14-17 N-terminal amino acids. These inhibitors were identified as oncostatin M (OSM), leukemia inhibitory factor (LIF), and transforming growth factor beta1 (TGF-beta1). The identities of the three EC growth inhibitors were confirmed by demonstrating that recombinant human OSM, LIF, and TGF-beta1 were inhibitory in the same concentration range. Inhibition of EC proliferation by OSM was a newly described property of this cytokine. OSM was the most potent inhibitor with a half-maximal inhibition by recombinant material of 0.15-.2 ng/ml compared with 0.6-0.9 and 0. 9-1.0 ng/ml for LIF and TGF-beta1, respectively. The three factors inhibited basal, vascular endothelial cell growth factor-stimulated, and fibroblast growth factor 2-stimulated EC proliferation. Interleukin-6 and ciliary neurotrophic factor, two cytokines related structurally to OSM and LIF, were not active as EC growth inhibitors. It was concluded that macrophage-like cells secrete a variety of potent EC growth inhibitors and that one of these, OSM, is among the most potent EC growth inhibitors yet reported.
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PMID:Inhibition of endothelial cell growth by macrophage-like U-937 cell-derived oncostatin M, leukemia inhibitory factor, and transforming growth factor beta1. 879 67

Keratin K17, the myoepithelial keratin, is expressed in psoriasis but is not present in healthy skin. Psoriasis is associated with production of gamma interferon (IFN gamma), which induces the expression of keratin K17 by activating transcription factor STAT1. Our hypothesis states that the induction of K17 is specific for the inflammatory reactions associated with high levels of IFN gamma and activation of STAT1. One of the corollaries of the hypothesis is that the STAT1-activating cytokines should induce the expression of keratin K17, whereas those cytokines that work through other mechanisms should not. Furthermore, because the STAT activation pathway is dependent upon protein phosphorylation events, phosphorylation inhibitors should attenuate the induction of keratin K17, whereas protein phosphatase inhibitors should augment it. To test this hypothesis, we analyzed lesional samples of inflammatory diseases using immunofluorescence, transfected keratinocytes with K17 gene promoter DNAs in the presence of various cytokines, and followed nuclear translocation of STAT1 in keratinocytes using specific antibodies. Confirming the hypothesis, we found that K17 is induced in psoriasis and dermatitis caused by delayed type hypersensitivity, which are associated with high levels of IFN gamma, but not in samples of atopic dermatitis, which is not. Two cytokines, interleukin-6 and leukemia inhibitory factor, which can induce phosphorylation of STAT1, can also induce K17 expression, whereas interleukin-3, interleukin-4, interleukin-10, and granulocyte macrophage colony stimulating factor have no effect on K17 expression. As expected, staurosporine and genistein inhibited, whereas okadaic acid augmented, the induction of K17 by IFN gamma. Our data indicate that in inflammatory skin diseases, lymphocytes, through the cytokines they produce, differently regulate not only each other, but also keratin gene expression in epidermis one of their target tissues.
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PMID:Regulation of epidermal expression of keratin K17 in inflammatory skin diseases. 882 63

Interleukin-6 (IL-6), a multipotential cytokine, initiates signal transduction pathways similar to those of ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF). These molecules share the signal transducing receptor component, gp130. IL-6 triggers homodimerization of gp130, whereas CNTF and LIF induce heterodimerization of gp130 and LIF receptor. Although CNTF or LIF treatment attenuates motor deficits in wobbler mouse motor neuron disease (MND), neuroprotective effects of IL-6 on this animal have not yet been clarified. Here we studied whether simultaneous treatment with IL-6 and soluble IL-6 receptor (sIL-6R) can ameliorate symptomatic and neuropathological changes in wobbler mouse MND. After clinical diagnosis at postnatal age 3-4 weeks, wobbler mice received subcutaneous injection with human recombinant IL-6 (1.0 mg/kg), human sIL-6R (0.5 mg/kg), IL-6 + sIL-6R or vehicle, daily for 4 weeks in a blind fashion. Compared to vehicle, coadministration with IL-6 and sIL-6R potentiated grip strength, attenuated muscle contractures in the forelimbs, reduced denervation muscle atrophy and prevented degeneration of spinal motor neurons. Single administration with IL-6 or sIL-6R did not retard the symptomatic and neuropathological progression, although IL-6-treated mice did not raise anti-IL-6 antibodies. Treatment with IL-6 + sIL-6R, but not with IL-6 or sIL-6R alone delayed progression of wobbler mouse MND. Our results indicate that the neuroprotective mechanism for IL-6/sIL-6R on wobbler mouse MND differs from that of CNTF or LIF alone. We hypothesize that IL-6/sIL-6R complex may function on motor neurons through activation and homodimerization of gp130.
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PMID:Coadministration of interleukin-6 (IL-6) and soluble IL-6 receptor delays progression of wobbler mouse motor neuron disease. 883 49

Ciliary neurotrophic factor (CNTF), a multipoietic factor, on a variety of neurons, prevents axotomy-induced motoneuron loss and can improve the outcome of murine motor neuron disease (MND). We carried out a study to determine whether other cytokines rescue spinal motoneurons from axotomy-induced cell death. Unilateral sciatic nerve was transected in neonatal rats. Two doses of recombinant murine cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF), recombinant rat CNTF, recombinant human granulocyte-colony stimulating factor (G-CSF), recombinant human interleukin-6 (IL-6), recombinant human tumor necrosis factor beta (TNF beta), or vehicle were administered daily for 2 weeks by intraperitoneal injection. After treatment, the number of spinal motoneurons was determined at the level of L4-5 segments. In comparison with vehicle, the higher doses of CDF/LIF, CNTF, and IL-6, and the lower doses of CDF/LIF and IL-6 significantly retarded the loss of motoneurons. G-CSF and TNF beta failed to inhibit motoneuron death. CDF/LIF and IL-6 rescued motoneurons from the retrograde death following axotomy, in a similar manner to CNTF. These results provide evidence that several cytokines may have therapeutic potential in human axonopathy or MND.
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PMID:Neuroprotective effect of various cytokines on developing spinal motoneurons following axotomy. 886 65

We examined the effects of an interleukin-6 related cytokine, leukemia inhibitory factor (LIF), on myocardial cells using cultured murine cardiac myocytes. LIF stimulation (1 x 10(3) U/ml) for 36 h increased the cell size of neonatal cardiac myocytes and increased [3H] leucine incorporation in both fetal and neonatal cardiac myocytes; the increase was more significant in fetal myocytes. LIF stimulation also increased the expression of c-fos mRNA, one of the immediate early genes. In addition, the expression of prepro-atrial natriuretic factor mRNA, one of the genes expressed in fetal myocardium and reactivated by hypertrophic stimulation, was increased after 48 h of incubation with LIF. LIF receptor mRNA was expressed in fetal, neonatal and adult murine hearts and cultured murine cardiac myocytes. LIF induced the tyrosine phosphorylation of gp130 within 15 min after it was added to cardiac myocytes. In addition, LIF mRNA was expressed in both cardiac myocytes and non-myocardial cells derived from hearts. These results suggest that LIF activates gp130 and induces myocardial hypertrophy by acting as an autocrine/paracrine factor in cardiac myocytes.
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PMID:Leukemia inhibitory factor induces a hypertrophic response mediated by gp130 in murine cardiac myocytes. 888 86

Cytokines play a major role in the pathophysiology of sepsis and septic shock. Using enzyme immunoassays the acute serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and leukemia inhibitory factor (LIF) were investigated in 90 patients with positive blood cultures and clinical signs of infection. In 27 patients samples were obtained on admission, after 1, 4, 12, 18, and 24 h, and then daily. The acute serum levels of IL-6, TNF-alpha, G-CSF, and IL-8 were significantly higher among patients with severe sepsis. Patients with Gram-negative infection had significantly higher levels of TNF-alpha on admission than did patients with Gram-positive infections (p = 0.0008). The levels of IL-6, G-CSF and, to some extent, TNF-alpha decreased rapidly in survivors within the first 24 h of admission to hospital and institution of treatment. LIF was detected in 8/90 in both survivors and nonsurvivors.
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PMID:Dynamics of blood cytokine concentrations in patients with bacteremic infections. 889 5

An exogenous supply of hematopoietic cytokines is essential for maintaining murine embryonic stem (ES) cells in a proliferative yet undifferentiated state. Recently, it was demonstrated that hematopoietic cytokines utilize the gp130 signal transduction pathway to maintain this phenotype, although their involvement toward maintaining porcine ES cell pluripotency has not been established. Therefore, the objective of this study was to determine the effectiveness of several heterologous hematopoietic cytokines at maintaining the isolated porcine inner cell masses (pICM) in an undifferentiated state. pICMs (day 7) were isolated by immunosurgery and cultured 4 days in one of six treatments: control medium, human leukemia inhibitory factor (hLIF; 1,000 mu/ml), human interleukin-6 (hIL-6; 100 ng/ml), hIL-6 + hIL-6 soluble receptor (hIL6 + sR; 100 ng/ml + 2.5 micrograms/ml), human oncostatin M (hOSM; 100 ng/ml), or rat ciliary neurotrophic factor (rCNTF; 100 ng/ml). All cytokines were prepared in Dulbecco's Modified Eagle's Medium/Ham's F-10 (1:1)-based medium. Morphology of pICMs was evaluated on a scale of 1 (fully undifferentiated) to 5 (fully differentiated) at 24-h intervals. Differentiation was significantly lower on day 2 for rCNTF vs. hLIF cultured pICMs (2.07 +/- 0.15 vs. 2.70 +/- 0.16; P < 0.05). Furthermore, addition of rCNTF gave the lowest overall mean differentiation score (2.53 +/- 0.15). However, none of the cytokines significantly delayed differentiation over controls for the 4-day culture period (P > 0.05). Since these heterologous cytokines were unable to inhibit differentiation, it is unlikely they will be beneficial towards isolating porcine ES cell lines under current conditions. Future work with homologous cytokines and dose effects may prove more beneficial.
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PMID:Effects of heterologous hematopoietic cytokines on in vitro differentiation of cultured porcine inner cell masses. 891 70

The interleukin-6 (IL-6) family of cytokines activates signaling through the formation of either gp130 homodimers, as for IL-6, or gp130-leukemia inhibitory factor receptor (LIFR) heterodimers as for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor, oncostatinM, and cardiotrophin-1. Recent in vitro studies with IL-6 and CNTF have demonstrated that higher order hexameric receptor complexes are assembled in which signaling chain dimerization is accompanied by the dimerization of both the cytokine molecule and its specific receptor alpha subunits (IL-6Ralpha or CNTFRalpha, respectively). IL-11 is a member of the IL-6 family and known to require gp130 but not LIFR for signaling. In this study we investigate the functional and biochemical composition of the IL-11 receptor complex. The human IL-11 receptor alpha-chain was cloned from a human bone marrow cDNA library. IL-11Ralpha was shown to confer IL-11 responsiveness to human hepatoma cells either by cDNA transfection or by adding a soluble form of the receptor (sIL11Ralpha) expressed in the baculovirus system to the culture medium. In vitro immunoprecipitation experiments showed that sIL11Ralpha specifically binds IL-11 and that binding is enhanced by gp130. Similarly to IL-6 and CNTF, gp130 is able to induce dimerization of the IL-11.IL-11Ralpha subcomplex, the result of which is the formation of a pentameric receptor complex. However, in contrast to the other two cytokines, IL-11 was unable to induce either gp130 homodimerization or gp130/LIFR heterodimerization. These results strongly suggest that an as yet unidentified receptor beta-chain is involved in IL-11 signaling.
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PMID:Functional expression of soluble human interleukin-11 (IL-11) receptor alpha and stoichiometry of in vitro IL-11 receptor complexes with gp130. 894 87

Oxytocin (OT) has been shown to be the dominant peptide of the neurohypophysial family expressed by thymic epithelial and nurse cells (TEC/TNC) in various species. Thymic OT is not secreted but, after translocation of a hybrid neurophysin/MHC class I protein, is integrated within the plasma membrane of TEC, thus allowing its presentation to pre-T cells. In order to further demonstrate that thymic OT behaves like a membrane antigen, we assessed the effect of mAbs to OT on cytokine productions by cultures enriched in human TEC. 75-85% pure TEC cultures were prepared from human thymic fragments. Using immunofluorescence and confocal microscopy, ir-OT, ir-interleukin-1 beta (IL-1 beta), ir-interleukin-6 (IL-6) and ir-leukemia inhibitory factor (LIF) could be detected in these TEC cultures. ir-OT was restricted to TEC, while some ir-IL-6 and ir-LIF were also seen in occasional fibroblasts. In basal conditions, ir-IL-6 and ir-LIF (but not ir-OT and ir-IL-1 beta) were detected in the supernatants of human TEC cultures. MAbs to OT induced a marked increase of ir-IL-6 and ir-LIF secretion in TEC cultures. No significant effect was observed using mAbs against vasopressin, mouse immunoglobulins, or control ascitic fluid controls. These data show that OT is fully processed and recognized by specific mAbs at the outer surface of TEC plasma membrane. They further support that thymic OT behaves as the self-antigen of the neurohypophysial family.
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PMID:Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen. 895 4


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