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)

C57Bl/10 ScSn mice infected with Toxoplasma gondii developed a meningoencephalitis, characterized by areas of tissue destruction and cellular infiltration including foci of neutrophils. Large numbers of cyst stages were found throughout the brain but were not always associated with inflammation. The use of immunocytochemistry to detect glial fibrillary acidic protein, an astrocyte specific marker, showed a widespread astrocyte activation. This was particularly prominent in areas of intense inflammation but cysts were negative for glial fibrillary acidic protein, indicating that astrocytes were not host cells for the bradyzoites. The use of the polymerase chain reaction to assist in the amplification of total brain RNA allowed the characterization of the cytokines being produced locally within the brains of infected animals. beta-actin transcripts were detected in all of the uninfected and infected mice. In only one of the seven uninfected control mice were other transcripts found. Transcripts for tumour necrosis factor-alpha, interleukin-1 alpha and beta, interleukin-6, macrophage inflammatory protein-1 and interferon-gamma as well as the CD4 marker were detected in all of the infected mice. However, transcripts for IL-2 and IL-4 were not present. Several of the cytokines present are capable of initiating meningeal inflammation and may play a role in the immunopathogenesis of toxoplasmic encephalitis.
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PMID:Detection of cytokine mRNA in the brains of mice with toxoplasmic encephalitis. 143 33

Malignant gliomas are characteristically surrounded by marked gliosis. To assess whether glioma-derived products contribute to the proliferation of astrocytes, a feature of the gliosis response, we evaluated the influence of culture supernatants from malignant human glioma lines and tumor cyst fluids collected from two patients with glioblastoma multiforme on the proliferation of non-transformed adult human astrocytes. Both the culture supernatants and cyst fluids significantly increased DNA synthesis in astrocytes as assessed by a double immunofluorescence glial fibrillary acidic protein-bromodeoxyuridine technique. The net proliferative effect mediated by glioma cell line supernatants was tumor growth phase-dependent, being preferentially expressed during the logarithmic phase of glioma cell growth. Specific growth factor molecules and cytokines known to be secreted by gliomas (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, interleukin-6, and tumor necrosis factor-alpha) could not reproduce the mitogenic effects of the glioma-derived soluble factors. Cytokines which can induce DNA synthesis by adult human astrocytes in vitro, gamma-interferon and interleukin-1, were not detected in the culture supernatant of glioma lines used in this study. In conjunction with the documented effects of glioma products on endothelial and lymphoid cells, the current study suggests that soluble glioma products can contribute to the production of surrounding gliosis observed in vivo.
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PMID:Malignant glioma-derived soluble factors regulate proliferation of normal adult human astrocytes. 151 71

The proliferation and differentiation of astrocytes are fundamental events in the normal development and function of the central nervous system (CNS), and may also contribute to the pathogenesis of a number of neurological diseases. Products of T lymphocytes can stimulate proliferation of astrocytes, but the nature of the T lymphocyte-derived molecule(s) responsible for this response is unknown. The present study was undertaken to examine several well-characterized T lymphocyte-derived factors for their ability to stimulate cultured primary rat astrocytes. While recombinant human interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), and rat or human recombinant interferon-gamma (IFN-gamma) have no proliferative effect on astrocytes, a human T cell-derived B cell growth factor (BCGF) does. This BCGF, termed 2B11, had previously been characterized by its ability to enhance the proliferation of anti-mu-stimulated human B cells, while not influencing B cell immunoglobulin synthesis. High performance liquid chromatography (HPLC)-purified 2B11-BCGF (MW approximately 20,000 daltons) stimulates the proliferation of astrocytes in a dose-dependent fashion. Purified 2B11-BCGF also induced morphological differentiation and increased mRNA transcripts for glial fibrillary acidic protein (GFAP) in rat astrocytes. In addition to demonstrating the absence of effect of other known lymphokines, the effect on astrocytes attributed to 2B11-BCGF was confirmed by blocking its activity with a monoclonal antibody specific for 2B11-BCGF. Absorption experiments demonstrated that when BCGF activity was absorbed out by large, activated human B cells, astrocyte-stimulatory activity was also depleted. Rat astrocytes were able to partially absorb out both BCGF and astrocyte-stimulatory activity. These results suggest that 2B11-BCGF is responsible for stimulating astrocyte proliferation, and that human B cells and rat astrocytes may share a similar receptor for BCGF. These findings indicate that the growth and differentiation of astrocytes can be influenced by a T cell-derived lymphokine, 2B11-BCGF, whose activity thus far appears to be distinct from other reported cytokines.
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PMID:Human B cell growth factor enhances proliferation and glial fibrillary acidic protein gene expression in rat astrocytes. 248 87

New rod photoreceptors are added to mature teleost retinas throughout life by regulated proliferation of rod precursor cells (RPCs). In this study, candidate regulators of RPC proliferation, acidic and basic fibroblast growth factors (aFGF and bFGF; 0.1 microgram/eye), interleukin-6 (IL-6; 0.1 microgram) and phytohaemagglutinin (HA15; 1.0 microgram), were injected intravitreally into one eye of goldfish (body length 5-6 cm), and mitotic RPCs in both retinas were detected and counted 3-50 days later by immunohistochemistry for proliferating cell nuclear antigen (PCNA). Retinal integrity after treatment was assessed by immunohistochemistry for tyrosine hydroxylase (TH) and other retinal antigens. All the agents applied altered the density of PCNA-immunoreactive (ir) cells in the outer and inner nuclear layers (ONL and INL) in both retinas as soon as 2-3 days after unilateral injection. Initially (2-20 days after injection), particularly in the treated retina, PCNA-ir cells appeared in clusters accompanied by various numbers of scattered individual cells, but subsequently the clusters of PCNA-ir cells disappeared while the density of singly distributed cells increased until 30 days after injection. At the doses given, these effects were most striking with aFGF and bFGF and less with IL-6 and HA15. In radial cryosections, other cellular elements immunoreactive to markers such as TH, serotonin, neuropeptide Y, substance P, glutamine synthetase, glial fibrillary acidic protein and protein kinase C, were found normal in terms of morphology. In addition, a monoclonal antibody (NN-2) was found to label some non-neuronal structures (macrophages, microglia and blood vessels) inside and outside the retina intoxicated with 6-hydroxydopamine, a few NN-2-ir cells being PCNA-positive. However, clustered PCNA-ir and marginal neuroblast cells were NN-2-negative. These results indicate that FGFs may play an important role in stimulating the proliferation of RPCs, for example, in the regeneration of fish retinas following neurotoxic destruction.
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PMID:Fibroblast growth factor induces proliferating cell nuclear antigen-immunoreactive cells in goldfish retina. 751 Mar 76

Recent evidence suggests that the level of interleukin-6 (IL-6) is elevated in Alzheimer's disease (AD) brains. IL-6 is produced by reactive glial cells and could potentially affect neuronal survival. Understanding the biochemical mechanism that regulates the production and release of IL-6 by astrocytic cells may help to identify potential targets for therapeutic intervention in AD. In the present study, glial fibrillary acidic protein-positive human U373MG astrocytoma cells were used as a model of reactive astrocytes. Production of IL-6 in response to drug treatment was monitored with an ELISA assay. Histamine (1-100 microM), substance P (SP; 1-100 nM), and human interleukin-1 beta (IL-1 beta; 1-30 pM) stimulated the release of IL-6 in a time- and concentration-dependent manner, with EC50 values of 4.5 microM, 8 nM, and 4.5 pM, respectively. The respective effects of histamine, SP, and IL-1 beta were effectively blocked by the histamine H1, SP, and IL-1 receptor antagonists, supporting a receptor-mediated event for these agents. Both histamine and SP enhanced the formation of inositol phosphates and increase intracellular calcium levels, suggesting that the phosphatidylinositol bisphosphate/protein kinase C pathway may be involved in the IL-6 release process. Indeed, phorbol 12-myristate 13-acetate, a protein kinase C activator, also evoked IL-6 release from the U373MG cells. On the other hand, IL-1 beta, which produces a much more robust release of IL-6 than histamine or SP, has no effect on inositol phosphate formation or intracellular calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the release of interleukin-6 from human astrocytoma cells. 751 68

We report pleiotropic actions of the interleukin-6 family of cytokines on a rat cerebral cortical oligodendrocyte cell line, Central Glia-4 (CG-4). This is a bipotential oligodendrocyte type-2 astrocyte (O-2A) progenitor cell line that can be manipulated in vitro to become either a type-2 astrocyte or to follow a linear sequence of events into becoming a mature oligodendrocyte. Using Northern and Western analyses in conjunction with immunocytochemistry we have demonstrated that ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and interleukin-6 (IL-6) cause a transient increase in glial fibrillary acidic protein (GFAP) in oligodendrocyte type-2 astrocyte (O-2A) progenitor cells. At maximal cytokine concentrations, the largest increase in GFAP protein levels were observed for CNTF and LIF; albeit, IL-6 did increase GFAP but the order of magnitude was 6-7 times less. Moreover, in trophic factor deprived medium, CNTF and LIF protected immature (O4+/MBP-) and mature (MBP+) oligodendrocytes from the apoptotic mode of cell death, while IL-6 had no effect in enhancing oligodendrocyte cell survival. Analysis of the cytokine-induced early response genes (ERGs) revealed a strong degree of overlap for CNTF and LIF. The effect of IL-6 was different in the degree to which the ERGs were up-regulated and in their temporal patterns of expression. These findings suggest that ERGs may be important, at least in part, for determining the extent of functional overlap observed within this cytokine family. Our findings clearly demonstrate differential regulation of oligodendrocyte survival and differentiation by the IL-6 family of cytokines.
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PMID:Regulation of an oligodendrocyte progenitor cell line by the interleukin-6 family of cytokines. 753 22

Tumor necrosis factor-alpha is a pluripotent cytokine that is reportedly mitogenic to astrocytes. We examined expression of the astrocyte intermediate filament component glial fibrillary acidic protein in astrocyte cultures and the U373 glioblastoma cell line after treatment with tumor necrosis factor-alpha. Treatment with tumor necrosis factor-alpha for 72 h resulted in a decrease in content of glial fibrillary acidic protein and its encoding mRNA. At the same time, tumor necrosis factor-alpha treatment increased the expression of the cytokine interleukin-6 by astrocytes. The decrease in glial fibrillary acidic protein expression was greater when cells were subconfluent than when they were confluent. Thymidine uptake studies demonstrated that U373 cells proliferated in response to tumor necrosis factor-alpha, but primary neonatal astrocytes did not. However, in both U373 cells and primary astrocytes tumor necrosis factor-alpha induced an increase in total cellular protein content. Treatment of astrocytes and U373 cells for 72 h with the mitogenic cytokine basic fibroblast growth factor also induced a decrease in glial fibrillary acidic protein content and an increase in total protein level, demonstrating that this effect is not specific for tumor necrosis factor-alpha. The decrease in content of glial fibrillary acidic protein detected after tumor necrosis factor-alpha treatment is most likely due to dilution by other proteins that are synthesized rapidly in response to cytokine stimulation.
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PMID:Tumor necrosis factor-alpha and basic fibroblast growth factor decrease glial fibrillary acidic protein and its encoding mRNA in astrocyte cultures and glioblastoma cells. 759 70

As both astrocytes and cytokines modulate the permeability of cerebral endothelial cells, transgenic animal models which overexpress cytokines, such as interleukin-6 (IL-6), may provide insight into the neuropathological consequences of increased BBB permeability. In this study, a GFAP-IL6 transgenic mouse model and horseradish peroxidase (HRP) were used to investigate BBB permeability and associated neuropathologic changes. In the cerebellum of control mice, the BBB developed between postnatal days 7 and 14. In transgenic mice, the BBB never developed and extensive breakdown was evident in both high- and low-expressor animals by 1 month after birth. Vascular proliferation was apparent from birth in association with development and retention of normal cerebellar architecture until 3 and 6 months in high- and low-expressor animals, respectively. At these times, a leptomeningeal inflammatory infiltrate, vacuolated astrocytic foot processes and endothelial abnormalities were apparent in the cerebellum. At 6 months in high-expressor and 12 months in low-expressor animals, parenchymal inflammation, gliosis, spongiform change, axonal degeneration and macrophage accumulation were evident. The findings suggest that increased production of IL-6 can influence the development and physiologic function of the BBB as well as contribute to parenchymal central nervous system injury.
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PMID:Evolution of neuropathologic abnormalities associated with blood-brain barrier breakdown in transgenic mice expressing interleukin-6 in astrocytes. 759 49

The reverse transcription and polymerase chain reaction technique (RT-PCR) was assessed for the quantification of changes in mRNA levels from primary astrocyte cultures. The effects of dibutyryl cyclic AMP (dBcAMP) on glial fibrillary acidic protein (GFAP) mRNA and the effects of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and lipopolysaccharide (LPS) on interleukin-6 (IL-6) mRNA were examined. Two quantitative PCR methods were used: one involved carrying out the reaction in the exponential phase and the other involved the coamplification of a competitive target sequence. Increased GFAP mRNA in response to chronic dBcAMP treatment and increased IL-6 mRNA in response to TNF-alpha/IL-1 beta were readily detected. Both RT-PCR techniques were found to be suitable for the detection of large as well as smaller (twofold) changes in mRNA levels. The advantages and limitations of RT-PCR for mRNA quantification are discussed.
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PMID:Reverse transcription and polymerase chain reaction technique for quantification of mRNA in primary astrocyte cultures. 769 77

The developmental potential of progenitors at two final stages of the macroglial lineage giving rise to oligodendrocytes in postnatal rat brain was studied in response to defined and serum inducers of astrocyte gene expression. Cell immunoselection [with Gd3 ganglioside, O4 and galactocerebroside (GalC) antibodies] was used to isolate G+D3O4- and O4+GalC- phenotypes directly from premyelinating cerebrum. In a basal defined culture medium, G+D3O4- progenitors differentiated infrequently into oligodendrocytes on a growth substratum comprised of meningeal cell-derived extracellular matrix. Their conversion into astrocytes, as determined by immunofluorescence analysis of glial fibrillary acidic protein expression, was induced by oncostatin-M as well as leukemia inhibitory factor (LIF) and ciliary neurotrophic factor, but not interleukin-6, and required extracellular matrix. By comparison, O4+GalC- progenitors were refractory to astrocyte induction under these conditions, as in short-term cultures of optic nerve, and differentiated into myelinogenic oligodendrocytes instead. Only in response to an overriding stimulus in fetal bovine serum did O4+GalC- progenitors, like their immediate precursors, become astrocytic. These data functionally distinguish two classes of astrocyte-inducing agents to provide clear evidence of an oligodendroblast, a progenitor defined by surface phenotype (O4+GalC-) and an altered response of the oligodendrocyte lineage to cytokines using signal transducer LIFR beta.
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PMID:Oligodendroblasts distinguished from O-2A glial progenitors by surface phenotype (O4+GalC-) and response to cytokines using signal transducer LIFR beta. 787 81


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