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)

Several cytokines are increased in psoriatic skin, mainly at the lesional level. Some of these mediators seem to be very important in the pathogenesis of psoriasis since they are thought to stimulate keratinocyte proliferation and/or to drive the inflammatory changes associated with psoriasis. Among the proinflammatory modulators, hematopoietins, which are a family of cytokines sharing a receptor component (the gp130 subunit), have been under intensive investigation in recent years. The hematopoietin family includes interleukin-6 (IL-6), interleukin-11 (IL-11,) leukemia inhibitory factor (LIF), oncostatin-M (OSM), granulocyte colony-stimulating factor (G-CSF), ciliary neurotrophic factor (CNTF) and cardiotrophin. Amounts of two of these molecules, IL-6 and IL-11, have been found to be increased in psoriatic lesions. The present study adds new information concerning the spontaneous release of two hematopoietins, namely LIF and OSM, in 48-h culture supernatants of lesional and nonlesional skin punch biopsies from psoriatic patients and normal subjects. The cytokine determinations were performed using commercially available ELISA kits. The results are expressed as picograms per milligram of tissue, after weight normalization. The levels of LIF released by lesional skin (median 2.4 pg/mg, range 0.05-13.4 pg/mg) were significantly higher than from nonlesional (median 0.4 pg/mg, range under detection limit (UDL)-4.4 pg/mg; P = 0.001) and normal skin (median 0.4 pg/mg, range UDL-0.9 pg/mg; P = 0.005). The OSM levels were also significantly higher in supernatants of lesional skin (median 0.9 pg/mg, range 0.4-5.2 pg/mg) than in supernatants of nonlesional (median 0.2 pg/mg, range UDL-0.8 pg/mg; P = 0.001) and normal skin (median 0.1 pg/mg, range UDL-0.4 pg/mg; P = 0.0001). In addition, interleukin-8 (IL-8), a cytokine involved in the pathomechanisms of psoriasis, showed a similar behaviour when measured in the same samples. Lesional skin showed a median value of 752.5 pg/mg, range 98.8-2063.8 pg/mg, nonlesional skin a median value of 58.3 pg/mg, range UDL-1252.5 pg/mg (P = 0.007) and normal skin a median value of 44.6 pg/mg, range UDL-176.7 pg/mg (P = 0.004). No significant differences were found between nonlesional and normal skin for the three molecules analyzed. Taken together with the fact that at least two other hematopoietins (namely IL-6 and IL-11) are also increased in supernatants of lesional psoriatic skin, these data point to a possible involvement of the hematopoietins in inflammatory processes associated with psoriasis.
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PMID:Spontaneous release of leukemia inhibitory factor and oncostatin-M is increased in supernatants of short-term organ cultures from lesional psoriatic skin. 952 95

Mice lacking thrombopoietin (TPO), or its receptor c-Mpl, display defective megakaryocyte and platelet development and deficiencies in progenitor cells of multiple hematopoietic lineages. The contribution of alternative cytokines to thrombopoiesis in the absence of TPO signalling was examined in mpl-/- mice. Analysis of serum and organ-conditioned media showed no evidence of a compensatory overproduction of megakaryocytopoietic cytokines. However, consistent with a potential role in vivo, when injected into mpl-/- mice, interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) retained the capacity to elevate megakaryocytes and their progenitors in hematopoietic tissues and increase circulating platelet numbers. However, double mutant mice bred to carry genetic defects both in c-Mpl and IL-3 or the alpha chain of the IL-3 receptor, displayed no greater deficiencies in megakaryocytes or platelets than mpl-deficient animals, suggesting absence of a physiologic role for IL-3 in the residual megakaryocytopoiesis and platelet production in these mice.
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PMID:Cytokine production and function in c-mpl-deficient mice: no physiologic role for interleukin-3 in residual megakaryocyte and platelet production. 953 84

Embryonic stem (ES) cells are pluripotent descendants of the inner cell mass of blastocysts capable of differentiating into progenitor cells of most if not all tissues. The pluripotency of ES cells is maintained by leukemia inhibitory factor (LIF), a member of the family of interleukin-6-type cytokines. These cytokines activate Janus tyrosine kinases and signal transducer and activator of transcription factors (Stat) via the signalling receptor component gp130. Pluripotent ES1 cells proliferating in the presence of LIF were known from previous studies to contain Stat3 and Stat1 capable of transcriptional activation. Here we report that the level of tyrosine-phosphorylated Stat3 decreases rapidly during differentiation induced by treatment of ES1 cells either with retinoic acid (RA) or by withdrawal of LIF. In line with this finding, the DNA-binding activity of Stat3 decreased during differentiation. In contrast, Stat5 was absent from pluripotent proliferating ES cells, but appeared early after induction of differentiation. The positive correlation between induction of differentiation and expression of Stat5 mRNA was confirmed for three independent ES cell lines. Stat5 transcripts were detectable in ES1 cells as early as 12 h after treatment with RA and 36 h after withdrawal of LIF. Stat5 protein was detectable 2 days after the onset of differentiation. These results establish Stat5 as a novel marker of very early stages of differentiation of ES cells.
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PMID:Transcription factor Stat5 is an early marker of differentiation of murine embryonic stem cells. 956 6

Oncostatin M (OSM) is a member of a family of cytokines that includes ciliary neurotrophic factor, interleukin-6, interleukin-11, cardiotrophin-1, and leukemia inhibitory factor (LIF). The receptors for these cytokines consist of a common signaling subunit, gp130, to which other subunits are added to modify ligand specificity. We report here the isolation and characterization of a cDNA encoding a subunit of the mouse OSM receptor. In NIH 3T3 cells (which endogenously express gp130, LIF receptor beta [LIFRbeta], and the protein product, c12, of the cDNA described here), mouse LIF, human LIF, and human OSM signaled through receptors containing the LIFRbeta and gp130 but not through the mouse OSM receptor. Mouse OSM, however, signaled only through a c12-gp130 complex; it did not use the LIF receptor. Binding studies demonstrated that mouse OSM associated directly with either the c12 protein or gp130. These data highlight the species-specific differences in receptor utilization and signal transduction between mouse and human OSM. In mouse cells, only mouse OSM is capable of activating the mouse OSM receptor; human OSM instead activates the LIF receptor. Therefore, these data suggest that all previous studies with human OSM in mouse systems did not elucidate the biology of OSM but, rather, reflected the biological actions of LIF.
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PMID:Cloning and characterization of a specific receptor for mouse oncostatin M. 958 76

In the present study, we characterized both temporal and spatial expression patterns of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) messenger ribonucleic acids (mRNAs) in injured skeletal muscle using in situ hybridization. LIF and IL-6 mRNAs were expressed in mononucleated cells and damaged muscle cells. Further, signals for LIF mRNA were also detected in Schwann cell-like cells of intramuscular nerves. These results suggest that the earliest events involved in the repair of injured muscles and nerves may be triggered by these cytokines.
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PMID:Localization of leukemia inhibitory factor and interleukin-6 messenger ribonucleic acids in regenerating rat skeletal muscle. 958 42

Several studies on disease and treatment effects on neurohormones have been conducted with small numbers of patients, using one blood sample as representative of their states. The aim of this study was to assess the within-patient variability of plasma concentrations of several hormones and cytokines of recent interest, in patients with moderate heart failure and controlled stable background therapy over 3 weeks. Blood for neurohormone and cytokine assays was sampled in duplicate from 18 patients with moderate heart failure. After an initial visit, the patients were kept on stable therapy until the second blood sampling 21 +/- 3 days later. The plasma concentrations of several neurohormones (endothelin, renin, angiotensin II, aldosterone, norepinephrine) and cytokines (interleukin-6 (IL-6), interleukin-13 (IL-13), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and soluble receptor type I of tumour necrosis factor-alpha, (sTNF-RI) were measured with immunochemical methods. Some cytokines (IL-13, CNTF and LIF) were not detected. Despite clinically satisfactory ACE inhibition, circulating angiotensin II and aldosterone levels were still elevated in some patients, suggesting aldosterone escape. The between-visit agreement of plasma concentrations measured in duplicate was less than 35% for all circulating factors, except renin which showed a higher variability throughout the 3-week study period.
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PMID:Within-patient variability of hormone and cytokine concentrations in heart failure. 960 70

The mRNA expression of the neuropoietic cytokines, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptor components (CNTFRalpha, LIFRbeta, IL-6Ralpha and gp130) was examined in peripheral nerves after two different types of injury, crush and transection. The CNTF mRNA expression levels decreased after injury and remained low in the transected model, but recovered in 4 weeks in the crushed model. The LIF mRNA rapidly increased after damage and returned gradually to control levels. The IL-6 mRNA expression increased rapidly within 1 day after injury but dramatically decreased soon after. The CNTFRalpha mRNA levels gradually increased after nerve injury. LIFRbeta was expressed in the intact nerve and decreased slightly after injury. The IL-6Ralpha expression was observed faintly in the intact nerve and increased significantly soon after injury. There was also an increase in the expression of gp130. Although the temporal expression of these neuropoietic cytokines and receptors was extremely different, their pattern was similar between the crushed and transected models, except for CNTF. These results suggest that the expression of the ligands and receptors are differentially regulated after peripheral nerve injury, implying that each cytokine and signal transduction system has entirely distinctive functions in neuronal regeneration and repair.
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PMID:Differential temporal expression of mRNAs for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptors (CNTFR alpha, LIFR beta, IL-6R alpha and gp130) in injured peripheral nerves. 963 Jul 4

In this study, granulocyte colony-stimulating factor (GCSF) proteins were chosen as subjects for normal mode analysis. As helical cytokines with a four helix bundled type topology, they were classified into long chain and short chain groups by Sprang and Bazan. Normal mode calculations were also carried out with leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and growth hormone (GH) as members of the long chain group and GCSF and IL-2 and IL-4 as members of the short chain group. For the GCSF families it was found that the fluctuations in the helical region are smaller than in the loop region, and it is clear that on the whole the smaller fluctuation residues belong to a large hydrophobic core region. Thus, it can be imagined how the receptor binding sites approach the receptor within the normal time-scale of pico seconds. In addition, two similar domain-type motions in low frequency modes were found with proteins in the long chain group, although we never observed any sequence similarity in the two separate two-domain regions in each protein of the long chain group. On the other hand, these two domain-type motions were not clear in proteins of the short chain group.
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PMID:Dynamic structures of granulocyte colony-stimulating factor proteins studied by normal mode analysis: two domain-type motions in low frequency modes. 969 16

Oncostatin M (OM) is a member of the cytokine family which regulates the proliferation and differentiation of a variety of cell types and includes interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and granulocyte-colony stimulating factor (G-CSF). This family of proteins adopts a four-helix bundle fold with up-up-down-down topology and contains intramolecular disulfide bonds. Since an X-ray or NMR structure for OM is not currently available, a homology model for OM was determined from the X-ray structures of human growth hormone (hGH), LIF, and G-CSF where the alignment was based on secondary structure instead of sequence. The OM secondary structure was determined from NMR structural data, and the secondary structures for hGH, LIF, and G-CSF were obtained from the reported X-ray structures. The resulting homology model was refined using sequential NOE distance 13C restraints, chemical shift information, and a conformational database.
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PMID:Homology model for oncostatin M based on NMR structural data. 969 47

The transmembrane protein gp130 is a shared component of the receptor complexes for the interleukin-6 (IL-6)-type cytokines, which include IL-6, leukemia inhibitory factor (LIF) and oncostatin M (OSM). In addition to its role in the generation of high affinity receptors, gp130 is required for signal transduction by these cytokines. In the present study we have examined the role of the N-terminal located, extracellular immunoglobulin (Ig)-like module of gp130 in signal transduction by IL-6 and LIF. We have expressed wild-type human gp130 or three mutants in murine myeloid M1-UR21 cells that lack functional endogenous gp130 but express the IL-6 receptor (IL-6R) and the LIF receptor (LIFR). By measuring cellular responses, such as morphological changes upon differentiation, soft agar colony formation, and induction of tyrosine phosphorylation of the signal transducer and activator of transcription, STAT3, we show that signaling by IL-6, but not LIF, is significantly reduced by mutations in the Ig-like module of gp130. However, the binding of 125I-labeled IL-6 or LIF is not affected by these mutations. We also present evidence that the Ig-like module forms part of the epitope of an anti-gp130 monoclonal antibody that neutralizes the bioactivity of IL-6, but not of LIF or OSM. The data suggest that gp130-activation by IL-6 and LIF requires different regions of gp130, that the Ig-like module of gp130 may be required for IL-6-induced gp130 dimerization, and that the stoichiometry of the high affinity IL-6 receptor-complex differs from those of the receptor-complexes for LIF and OSM.
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PMID:The immunoglobulin-like module of gp130 is required for signaling by interleukin-6, but not by leukemia inhibitory factor. 971


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