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)

To investigate the relationships between the central nervous system and interleukins, ventral mesencephalic cells from embryonic 17-day-old rats were cultured for 3 days in vitro (DIV) and exposed to interleukin-1 beta (IL-1 beta), interleukin-3 (IL-3), or interleukin-6 (IL-6) for the following 2 or 3 DIV with or without 2 microM 1-methyl-4-phenylpyridinium (MPP+). Thus, the survival of and the MPP+ neurotoxicity against the dopaminergic neurons immunostained with anti-tyrosine hydroxylase antibody were examined. For the survival studies, IL-1 beta has been shown to have a survival-promoting effect on dopaminergic neurons. This effect is initiated at a concentration between 0.1 and 1 ng/ml. In contrast to the effect of IL-1 beta, IL-3 and IL-6 failed to increase the survival of dopaminergic neurons. In MPP+ neurotoxicity analysis, only IL-6 among the three interleukins studied here has been shown to attenuate the MPP+ neurotoxicity against dopaminergic neurons in a dose-dependent manner; this neuro-protective action is apparent at a concentration of 10 ng/ml. In addition, these three interleukins did not promote glial proliferation. These findings suggest that the effects of IL-1 beta and IL-6 on dopaminergic neurons are not mediated by glial proliferation, that IL-1 beta acts as a neurotrophic factor on dopaminergic neurons, and that IL-6 is capable of protecting dopaminergic neurons from the neurotoxicity of MPP+.
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PMID:Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons. 758 33

Using RT-PCR, the development profile of interleukin-6 (IL-6) and its receptor (IL-6R) mRNAs in rat brain was investigated. Our results indicate that IL-6 and IL-6R mRNAs are coexpressed and are developmentally regulated in a tissue-specific manner. Highest levels of both transcripts were detected in the adult hippocampus. Most pronounced developmental changes of IL-6 message levels were observed in the rat striatum increasing up to 8-fold. By contrast, in all other regions such as neocortex, hippocampus, cerebellum and pons/medulla oblongata only minor changes (2- to 3-fold) in IL-6 expression were seen. In most tissues IL-6 mRNA levels peaked at day 20. Marked induction of the receptor message levels was detected in the striatum, hippocampus and neocortex (8- to 10-fold) whereas no changes were observed in the cerebellum and the pons/medulla oblongata. The expression pattern of both genes in various brain areas during postnatal development strongly supports the concept of IL-6 as a candidate for a new neurotrophic factor.
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PMID:Expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) mRNAs in rat brain during postnatal development. 818 Jul 86

Glia cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, has been implicated in the survival, morphological and functional differentiation of midbrain dopaminergic neurons and motoneurons in vitro and in vivo. The factor may thus have utility in the treatment of various human neurodegenerative disorders. Mechanisms regulating expression of GDNF in normal and diseased brain as a possible means to increase the local availability of GDNF are only beginning to be explored. We have established and employed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to study and compare levels of expression of GDNF mRNA in several cell types and to investigate its regulation. GDNF expression was clearly evident in primary cultured astrocytes, the glioma B49 and C6 cell, but less pronounced in the Schwannoma RN22 cell lines. Little or no signal could be observed in neuroblastoma cell lines (IMR32, LAN-1) or the pheochromocytoma cell line PC12, emphasizing the glial character of this factor. Using the C6 cell line we found that fibroblast growth factor-2 (FGF-2; bFGF) can increase GDNF mRNA levels, whereas FGF-1, platelet-derived growth factor (PDGF), and vasoactive intestinal polypeptide (VIP) are apparently ineffective. Several other factors (forskolin, kainic acid, triiodothyronine dexamethasone, GDNF, TGF-beta 1, and interleukin-6) appear to have slightly negative effects on GDNF mRNA levels at the concentrations tested. To further explore the relationship between FGF-2 and GDNF, we also addressed the question whether GDNF, like FGF-2, may have an effect on C6 cell proliferation. We conclude that (1) glial and glial tumor cells, rather than neuronal cell lines, express GDNF, (2) that FGF-2 has a prominent inductive effect on GDNF expression and (3) that GDNF stimulates C6 cell proliferation. Finally, these data suggest that neurotrophic actions of FGF-2 in mixed glial-neuronal cell cultures might be mediated in part by GDNF.
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PMID:GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells. 888 50

Sciatic sensory afferents that retrogradely transport and accumulate leukaemia inhibitory factor (LIF) within their soma were characterized in the adult rat in vivo. Twenty-four percent of neurons within the L4 and L5 dorsal root ganglia accumulated biotinylated LIF following intraneural injection of the cytokine into the sciatic nerve. Labelled cell bodies were predominantly of small diameter (20.1 +/- 0.5 microm). Retrograde transport was eliminated by excess unlabelled LIF but not by the related cytokines, ciliary-derived neurotrophic factor (CNTF) and interleukin-6 (IL-6). Double labelling revealed that the majority (81%) of LIF-accumulating neurons were immunopositive for CGRP and 34% were immunopositive for the cell surface glycoconjugate IB4. Sixty-two percent of LIF-accumulating neurons were immunopositive for trkA. Our results demonstrate a group of small-diameter sensory neurons that retrogradely transport LIF, comprising cells that constitutively express neuropeptides and those likely to be peptide-deficient. LIF-accumulating neurons expressing trkA are also potentially responsive to nerve growth factor. It is likely that the LIF-accumulating neurons described in this study are nociceptive in function.
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PMID:Leukaemia inhibitory factor is retrogradely transported by a distinct population of adult rat sensory neurons: co-localization with trkA and other neurochemical markers. 921 8

Over the past few years, it has been reported that physical and psychological stress elevate plasma interleukin-6 (IL-6), and that neural cells can produce IL-6 and have receptors for IL-6 (IL-6R). However, it is unknown whether IL-6 plays a role in regulating the functions of neural cells in response to stress. We demonstrated recently, using the reverse transcriptase-polymerase chain reaction (RT-PCR), that the levels of mRNAs for IL-6 and IL-6R in the rat brain are changed by restraint stress for four hours. In the present study, we investigated the expression of mRNAs for IL-6 and the IL-6R in the rat hypothalamus and midbrain during restraint stress. After rats had been restrained for 10, 30, 60, 120 or 240 min, the hypothalamus and midbrain were removed immediately and levels of IL-6 mRNA and of IL-6R mRNA in these regions were determined by RT-PCR. The expression of mRNAs for IL-6 and IL-6R in both regions was reduced after short-term (30-60 min) restraint stress and tended to return toward the control level after 120 min restraint stress. After long-term (240 min) restraint stress, the level of IL-6 mRNA was significantly increased in the midbrain, while the level of IL-6R mRNA was significantly reduced in both regions. These findings suggest that the need for IL-6 might decline after short-term restraint stress and, moreover, that the synthesis and secretion of IL-6 might be enhanced and IL-6 might be needed as a neurotrophic factor in the midbrain after long-term stress.
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PMID:The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R) in the rat hypothalamus and midbrain during restraint stress. 965 Nov 20

To investigate when the neurotrophic cytokines ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), oncostatin-M (OSM), interleukin-6 (IL-6) and cardiotrophin-1 (CT-1) act on developing sensory neurones and whether they co-operate with neurotrophins in regulating neuronal survival, we studied the in vitro trophic effects of these factors on two well-characterized populations of cranial sensory neurones at closely staged intervals throughout embryonic development. The cutaneous sensory neurones of the trigeminal ganglion, which show an early, transient survival response to BDNF and NT3 before becoming NGF-dependent, were supported by CNTF, LIF, OSM and CT-1 during the late fetal period, several days after the neurones become NGF-dependent. At this stage of development, these cytokines promoted the survival of a subset of NGF-responsive neurones. The enteroceptive neurones of the nodose ganglion, which retain dependence on BDNF throughout fetal development, were supported throughout their development by CNTF, LIF, OSM and CT-1, and displayed an additional survival response to IL-6 in the late fetal period. These findings indicate that populations of sensory neurones display different developmental patterns of cytokine responsiveness and show that embryonic trigeminal neurones pass through several phases of differing neurotrophic factor survival requirements.
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PMID:Cytokines promote the survival of mouse cranial sensory neurones at different developmental stages. 974 28

There are various neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and interleukin-6 (IL-6), which are essential for the promotion of neuronal survival (prevention of apoptosis), differentiation and regeneration in the central nervous system. Neurotrophic factors, neurotrophic factor-like substances and inducers of neurotrophic factor biosynthesis have enormous therapeutic potential for serious neuronal diseases such as Alzheimer's disease or traumatic, chemical and ischemic lesions in the brain. The clarification of the mechanism in neurotrophic factor biosynthesis is important in understanding the development of the drugs that stimulate neurotrophic factor production. In this review, we describe these mechanisms in the biosynthesis of NGF, BDNF, GDNF and IL-6, and also discuss the drugs that could possibly promote neurotrophic factor biosynthesis. (c) 2002 Prous Science. All rights reserved.
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PMID:The Signaling Pathway of Neurotrophic Factor Biosynthesis. 1267 25

Possible strategies for treating ischaemic stroke include: (i) neuroprotection (preventing damaged neurons from undergoing apoptosis in the acute phase of cerebral ischaemia), and (ii) neurosupplementation (the repair of broken neuronal networks with newly born neurons in the chronic phase of cerebral ischaemia). In this paper, we review our recent progress in development of these distinct new strategies for treatment of damaged brain following a stroke. Firstly, we investigated the role of endogenous IL-6 (interleukin-6), which is one of the cytokines drastically induced by ischaemic stimuli, by administering IL-6RA (anti-IL-6 receptor monoclonal antibody) to mice. We found that endogenous IL-6 plays a critical role in neuroprotection and that its role may be mediated by STAT3 (signal transducer and activator of transcription-3) activation. Secondly, we studied the endogenous sources of the newly born neurons in the ischaemic striatum by region- and cell-type-specific cell labelling techniques. The results revealed that the SVZ (subventricular zone) is the principal source of the neuronal progenitors that migrate laterally towards the infarcted regions, and differentiate into newly born neurons. Finally, we developed a restorative stroke therapy with a bio-affinitive scaffold, which is an appropriate poly-porous structure releasing bioactive substances such as neurotrophic factor. This bio-affinitive scaffold is able to give an appropriate environment for newly born neurons. In future, we will combine these strategies to develop more effective therapies for treatment of strokes.
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PMID:Neuroprotection and neurosupplementation in ischaemic brain. 1707 9

Selegiline inhibits the activity of monoamine oxidase B, enhances the release of dopamine, blocks the uptake of dopamine, acts as a calmodulin antagonist, and enhances the level of cyclic AMP, which in turn protects dopaminergic neurons. It possesses cognition-enhancing functions, rejuvenates serum insulin-like growth factor I in aged rats, and enhances life expectancy in rodents. Selegiline possesses neurotrophic-like actions, and rescues axotomized motorneurons independent of monoamine oxidase B inhibition. It enhances the synthesis of nerve growth factor, protects dopaminergic neurons from glutamate-mediated neurotoxicity, and protects dopaminergic neurons from toxic factors present in the spinal fluid of parkinsonian patients, and the said effect may be mediated via elaborating brain derived neurotrophic factor. Selegiline increases the striatal superoxide dismutase, protects against peroxynitrite- and nitric oxide-induced apoptosis, and guards dopaminergic neurons from toxicity induced by glutathione depletion. It stimulates the biosynthesis of interleukin 1-beta and interleukin-6, is an immunoenhancing substance, possesses antiapoptotic actions, and is neuroprotectant in nature. Selegiline has been shown to be efficacious in Parkinson's disease, global ischemia, Gille de la Tourette syndrome, and narcolepsy. Its therapeutic efficacy in Alzheimer's disease remains uncertain. In Alzheimer's disease, short term studies of selegiline suggest a beneficial effect; whereas long term studies are less convincing.
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PMID:Therapeutic efficacy of selegiline in neurodegenerative disorders and neurological diseases. 1710 May 91

Studies have shown that cytokines released following CNS injury can affect the supportive or cytotoxic functions of microglia. Interleukin-6 (IL-6)-family cytokines are among the injury factors released. To understand how microglia respond to IL-6 family cytokines, we examined the effects of ciliary neurotrophic factor (CNTF) and IL-6 on primary cultures of rat microglia. To assess the functional state of the cells, we assayed the expression of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and cyclooxygenase 2 (COX-2) following stimulation. We show that CNTF reduces COX-2 levels, whereas IL-6 increases the expression of IL-1beta, TNFalpha, and Cox-2. We also examined trophic factor expression and found that CNTF enhances glial cell-line derived neurotrophic factor (GDNF) mRNA and protein secretion, whereas IL-6 has no effect. Correspondingly, conditioned media from CNTF-stimulated microglia promote motor neuron survival threefold beyond controls, whereas IL-6-stimulated microglia decrease neuronal survival twofold. To understand better the signaling mechanisms responsible for the opposite responses of these IL-6-family cytokines, we examined STAT-3 and ERK phosphorylation in CNTF- and IL-6-stimulated microglia. IL-6 markedly increases STAT-3 and ERK phosphorylation after 20 min of treatment, whereas these signal transducers are weakly stimulated by CNTF across a range of doses. We conclude that CNTF modifies microglial activation to support neuronal survival and that IL-6 enhances their capacity to do harm, as a result of different modes of intracellular signaling.
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PMID:Ciliary neurotrophic factor and interleukin-6 differentially activate microglia. 1821 91


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