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)

Tumor necrosis factor (TNF) has a specific gene-inducing activity on many cell types and exerts a cytotoxic effect on a number of tumor cell lines. However, several tumor cell types are resistant to TNF-induced effects, and some of these produce TNF. We previously demonstrated that introduction of an exogenous TNF gene in the TNF-sensitive cell line L929sA induced autocrine TNF production and unresponsiveness to the cytotoxic activity of TNF. This resistance required biologically active TNF and was correlated with complete down-modulation of the TNF receptors on the cell surface. We have now characterized this process in more detail. The role of expression of the membrane-bound TNF proform and its subsequent proteolytic processing in the induction of TNF unresponsiveness was investigated. Exchange of the TNF presequence for the signal sequence of interleukin-6 resulted in production of secreted TNF, but not in induction of TNF resistance. On the other hand, expression of non-secretable, membrane-bound TNF generated complete TNF unresponsiveness. To explore whether the requirement for anchoring reflected a specific functional role of the TNF presequence, the latter was replaced by the membrane anchor of trimeric chicken hepatic lectin. Expression of this construct induced complete TNF unresponsiveness. Hence, the role of the TNF presequence in the induction of TNF unresponsiveness only involves its function as a membrane anchor, which permits oligomerization of the TNF molecule into a biologically active homotrimer.
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PMID:Induction of unresponsiveness to tumor necrosis factor (TNF) after autocrine TNF expression requires TNF membrane retention. 945 42

Interleukin-6 may play an essential role in early inflammatory processes as response to degenerating cholinergic cells in the nucleus basalis of Meynert in patients suffering Alzheimer's disease. The cholinergic immunotoxin, 192IgG-saporin, was applied to produce selective and specific degenerations of basal forebrain cholinergic cells. To disclose the lesion-induced temporal cascade of the expression pattern of IL-6, and to reveal the cellular source for production and secretion of IL-6 in vivo after endogeneously induced basal forebrain cholinergic cell loss, both in situ hybridization and immunocytochemistry for IL-6 were performed. To identify the cell types expressing IL-6 mRNA, double labeling techniques were applied combining in situ hybridization technique with immunocytochemistry and lectin histochemistry for both micro- and astroglia and a number of neuronal markers including choline acetyltransferase, parvalbumin, and neurofilaments. In the intact brain, IL-6 is mainly localized in neurons, in particular in both cholinergic and GABAergic neurons of the basal forebrain. Although basal forebrain cholinergic lesion resulted in a dramatic increase in the number of micro- and astroglial cells at the lesion site, IL-6 expression could not be detected in any of the lesion-induced activated glial cell types. Moreover, cholinergic lesion led to a reduced number of IL-6-expressing cells in the basal forebrain, which is assumed to be due to the loss of cholinergic cells. The predominantly neuronal localization in rat brain suggests a role for IL-6 in activating micro- and astroglial cells in response to degenerating cholinergic neurons.
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PMID:Interleukin-6 is not expressed in activated microglia and in reactive astrocytes in response to lesion of rat basal forebrain cholinergic system as demonstrated by combined in situ hybridization and immunocytochemistry. 946 76

The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immunogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis. The whole protein and its two fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects. Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-gamma), IL-12, and IL-10 but not IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-gamma was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-gamma upon in vitro stimulation of CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae. Their enhanced susceptibility was attributable to the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise either Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.
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PMID:A 70-kilodalton recombinant heat shock protein of Candida albicans is highly immunogenic and enhances systemic murine candidiasis. 957 2

Human leukemic early T cells of the HSB.2 line coexpress the EP2, EP3 and EP4 subtypes of prostaglandin E2 (PGE2) receptors (Rs). EP3 Rs have previously been demonstrated to transduce PGE2 stimulation of secretion of matrix metalloproteinase (MMP)-9 by HSB.2 T cells through Ca++-dependent enhancement of MMP-9 mRNA transcription. We now show that PGE2 and the EP4/EP2/EP3 R-selective agonist misoprostol, but not the EP3 R-directed agonists sulprostone and M&B28767, induced increases in HSB.2 T cell interleukin-6 (IL-6) mRNA and secretion. Pharmacological agents that increase intracellular concentration of cyclic AMP ([cAMP]i) mimicked and synergistically enhanced induction of IL-6 secretion by PGE2, whereas inhibitors of protein kinase A (PKA) but not protein kinase C suppressed PGE2-evoked increases in IL-6 secretion, suggesting that cAMP and PKA are the intracellular messengers of the PGE2 effect. Exposure of HSB.2 T cells to the mitogenic lectin concanavalin A (Con A) increased basal IL-6 secretion, without a change in IL-6 mRNA level. Con A-stimulated HSB.2 T cells responded to PGE2 with greater increases in IL-6 mRNA and secretion of IL-6. Con A also down-regulated mRNA encoding both EP3 Rs and EP2 Rs, and concurrently up-regulated mRNA encoding EP4 Rs of HSB.2 T cells. Therefore, EP4 and EP2 Rs mediate PGE2-induced increases in IL-6 secretion by HSB.2 T cells through a transcriptional and cAMP dependent-mechanism. The increased ratio of EP4 Rs/EP3 Rs may contribute to Con A enhancement of PGE2-elicited increases in IL-6 secretion by HSB.2 T cells.
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PMID:EP4/EP2 receptor-specific prostaglandin E2 regulation of interleukin-6 generation by human HSB.2 early T cells. 973 6

Changes of glycosylation of serum proteins of patients with psoriatic arthritis were detected by lectin blotting and a new enzyme-linked lectin assay (ELLA) using concanavalin A (Con A). A good linear correlation was found between the total Con A-reactivity of serum and the serum levels of C-reactive protein and interleukin-6, which is known to regulate the glycosylation pattern of proteins upon inflammation. A good linear correlation was also observed between the immunoreactivity of alpha 1-antitrypsin, measured by ELISA, using a monoclonal antibody sensitive to glycosylation changes, and the erythrocyte sedimentation rate and the serum concentrations of soluble interleukin-2 receptor, an index of lymphocyte activation which correlated with some inflammatory parameters of disease activity. These protein changes, which are described here for the first time, deserve to be studied in further detail in view of their possible clinical applications.
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PMID:Changes of glycosylation of serum proteins in psoriatic arthritis, studied by enzyme-linked lectin assay (ELLA), using concanavalin A. 986 40

Leukemia inhibitory factor (LIF) is a multifunctional cytokine belonging to the interleukin-6 subfamily of helical cytokines, all of which use the glycoprotein (gp) 130 subunit for signal transduction. The specific receptor for LIF, gp190, binds this cytokine with low affinity and is also required for signal transduction. We have recently reported that glycosylated LIF produced by transfected Chinese hamster ovary cells also binds to a lectin-like receptor, mannose 6-phosphate/insulin-like growth factor II receptor (Man-6-P/IGFII-R) (Blanchard, F., Raher, S., Duplomb, L., Vusio, P., Pitard, V., Taupin, J. L., Moreau, J. F., Hoflack, B., Minvielle, S., Jacques, Y., and Godard, A. (1998) J. Biol. Chem. 273, 20886-20893). The present study shows that (i) mannose 6-phosphate-containing LIF is naturally produced by a number of normal and tumor cell lines; (ii) other cytokines in the interleukin-6 family do not bind to Man-6-P/IGFII-R; and (iii) another unrelated cytokine, macrophage-colony-stimulating factor, is also able to bind to Man-6-P/IGFII-R in a mannose 6-phosphate-sensitive manner. No functional effects or signal transductions mediated by this lectin-like receptor were observed in various biological assays after LIF binding, and mannose 6-phosphate-containing LIF was as active as non-glycosylated LIF. However, mannose 6-phosphate-sensitive LIF binding resulted in rapid internalization and degradation of the cytokine on numerous cell lines, which suggests that Man-6-P/IGFII-R plays an important role in regulating the amounts of LIF available in vivo.
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PMID:Mannose 6-Phosphate/Insulin-like growth factor II receptor mediates internalization and degradation of leukemia inhibitory factor but not signal transduction. 1045 36

Although interleukin-6 (IL-6) has various neuroprotective effects against cerebral ischemia, the topographic distribution and cellular source of IL-6 after cerebral ischemia remain unclear. In the current study, the localization of IL-6 protein was immunohistochemically examined in rats after 3.5, 12, 24, and 48 hours of reperfusion after 1.5 hours of middle cerebral artery occlusion. Middle cerebral artery occlusion was induced by the intraluminal suture method. The specificity of the anti-IL-6 antibody used in the current study was confirmed by Western blot analysis and an immunoabsorption test. To identify the cellular source, lectin histochemical study and immunohistochemical study with microtubule-associated protein-2, ED1, and glial fibrillary acidic protein also were carried out. The sham group did not show any clear IL-6 immunoreactivity. After 3.5 hours of reperfusion, IL-6 immunoreactivity was first detected on the reperfused side, and it was upregulated, especially in the periinfarct region, after 24 hours of reperfusion. Also, IL-6 was expressed after 3.5 hours of reperfusion in the contralateral cerebral cortex and bilateral hippocampi. Double staining showed that the cells containing IL-6 were neurons and round-type microglia, not astrocytes. The current findings suggest that IL-6 expression in ischemically threatened neurons and reactive microglia is closely associated with brain tissue neuroprotective mechanisms against cerebral ischemia.
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PMID:Temporal profile and cellular localization of interleukin-6 protein after focal cerebral ischemia in rats. 1056 72

Cytokines are important intercellular messengers involved in neuron-glia interactions and in the microglial-astroglial crosstalk, modulating the glial response to brain injury and the lesion outcome. In this study, excitotoxic lesions were induced by the injection of N-methyl-D-aspartate in postnatal day 9 rats, and the cytokines interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha) and transforming growth factor beta 1 (TGF-beta1) analysed by ELISA and/or immunohistochemistry. Moreover, cytokine-expressing glial cells were identified by means of double labelling with glial fibrillary acidic protein or tomato lectin binding. Our results show that both neurons and glia were capable of cytokine expression following different patterns in the excitotoxically damaged area vs. the nondegenerating surrounding grey matter (SGM). Excitotoxically damaged neurons showed upregulation of IL-6 and downregulation of TNFalpha and TGF-beta1 before they degenerated. Moreover, in the SGM, an increased expression of neuronal IL-6, TNFalpha and TGF-beta1 was observed. A subpopulation of microglial cells, located in the SGM and showing IL-1beta and TNFalpha expression, were the earliest glial cells producing cytokines, at 2-10 h postinjection. Later on, cytokine-positive glial cells were found within the excitotoxically damaged area and the adjacent white matter: some reactive astrocytes expressed TNFalpha and IL-6, and microglia/macrophages showed mild IL-1beta and TGF-beta1. Finally, the expression of all cytokines was observed in the glial scar. As discussed, this pattern of cytokine production suggests their implication in the evolution of excitotoxic neuronal damage and the associated glial response.
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PMID:Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain. 1102 20

A method was developed for the determination of putative lectin activities of cytokines. It involved the immunoblotting measurement of the quantity of these cytokines unbound to a series of different immobilized glycoconjugates and displacement of the bound cytokines with oligosaccharides of known structures. This method allows demonstrating that the following interleukins specifically recognize different oligosaccharide structures in a calcium-independent mechanism: interleukin-1alpha binds to the biantennary disialylated N-glycan completed with two Neu5Acalpha2-3 residues; interleukin-1beta to a GM4 sialylated glycolipid Neu5Acalpha2-3Galbeta1-Cer having very long and unusual long-chain bases; interleukin-4 to the 1,7 intramolecular lactone of N-acetyl-neuraminic acid; interleukin-6 to compounds having N-linked and O-linked HNK-1-like epitopes; and interleukin-7 to the sialyl-Tn antigen. Because the glycan ligands are rare structures in human circulating cells, it is suggested that such activities could be essential for providing specific signaling systems to cells having both the receptors and the oligosaccharide ligands of the interleukin at their cell surface.
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PMID:Recombinant human interleukins IL-1alpha, IL-1beta, IL-4, IL-6, and IL-7 show different and specific calcium-independent carbohydrate-binding properties. 1105 99

An organotypic culture system of the early postnatal rat retina was developed to study microglial activation within a tissue environment. One day after tissue preparation, microglial cells of the ganglion cell/nerve fiber layer revealed features of activation. Cells acquired an ameboid morphology as revealed by Bandeiraea simplicifolia lectin staining. Proliferation-as revealed by Ki67 immunocytochemistry-resulted in higher cell densities. In the supernatant, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant factor-1 (MCP-1) were detected by using specific enzyme-linked immunosorbent assay systems, activated microglia being the most likely source of their release. After 6 days in vitro (div), microglial cells regained their resting morphology, and cell counts returned to control levels. Concomitantly, the release activity decreased to undetectable levels. When slices were treated at this later stage of cultivation (>6 div) with bacterial lipopolysaccharide (LPS; 100 ng/ml for 24 hours), microglial cells became activated, as revealed by a change in morphology. In parallel, the LPS treatment also resulted in high levels of TNF-alpha, IL-6, and MCP-1 in the culture medium. Both the release from the tissue and the morphological changes of the microglia were reversible. Seventy-two hours after LPS removal, only microglia with ramified morphology were found, and release activities returned to baseline. These data suggest that the organotypic culture of the retina is a useful model for studying microglial activation from its resting form.
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PMID:Characterization of microglial cells and their response to stimulation in an organotypic retinal culture system. 1117 1

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