Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes in the central nervous system (CNS) associate intimately with vascular endothelial cells and are integral to the blood-brain barrier (BBB). Leukocyte transmigration across the BBB is a cardinal feature of CNS inflammation, as observed in experimental autoimmune encephalomyelitis, and very late antigen-4 (VLA-4)/vascular cell adhesion molecule-1 (VCAM-1) interactions have recently been proposed as essential for this process. VCAM-1 expression by astrocytes was recently reported. We addressed the regulation of VCAM-1 expression by inflammatory cytokines in primary human astrocytes and two human astrocytoma cell lines. Astrocytoma cells up-regulated surface VCAM-1 expression in response to cytokines in the following order: IFN-gamma plus TNF-alpha > IFN-gamma plus IL-1 beta > TNF-alpha > IFN-gamma. Cytokine-activated astrocytoma cells expressed 7-domain VCAM-1, as indicated by accumulation of 3.2-kb VCAM-1 mRNA and immunoprecipitation of a 100-kDa protein with anti-VCAM-1 mAb. Lymphoblast adhesion to cytokine-activated astrocytoma cell monolayers was significantly blocked by mAb specific for VCAM-1 and VLA-4, indicating that astrocytoma cell VCAM-1 was functional. Astrocytoma cell expression of VCAM-1 could be a constituent of the astrocyte phenotype. To support this possibility, we demonstrated that cytokine-treated adult human and rat primary astrocytes expressed VCAM-1, and the rank order of cytokine potency for VCAM-1 induction in primary and neoplastic astrocytes was strikingly similar. This is the first documentation of VCAM-1 expression by adult human astrocytes. Expression of VCAM-1 by astrocytes at the BBB could play a role in mononuclear leukocyte entry into the CNS.
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PMID:Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines. 753 Jul 45

The kinetics of mRNA expression in the central nervous system (CNS) for a series of putatively disease-promoting and disease-limiting cytokines during the course of experimental autoimmune encephalomyelitis (EAE) in Lewis rats were studied. Cytokine mRNA-expressing cells were detected in cryosections of spinal cords using in situ hybridization technique with synthetic oligonucleotide probes. Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-beta (= lymphotoxin-alpha) and cytolysin appeared early and before onset of clinical signs of EAE; (ii) TNF-alpha peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-gamma (IFN-gamma) mRNA shown previously is consistent with a role of IL-12 in promoting proliferation and activation of T helper 1 (Th1) type cells producing IFN-gamma. The TNF-beta mRNA expression prior to onset of clinical signs favours a role for this cytokine in disease initiation. A pathogenic effector role of TNF-alpha was suggested from these observations that TNF-alpha mRNA expression roughly paralleled the clinical signs of EAE. This may be the case also for cytolysin. IL-10-expressing cells gradually increased to high levels in the recovery phase of EAE, consistent with a function in down-regulating the CNS inflammation. From these data we conclude that there is an ordered appearance of putative disease-promoting and -limiting cytokines in the CNS during acute monophasic EAE.
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PMID:Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta. 759 56

The interferons (IFNs) are a family of secretory glycoproteins possessing potent antiviral, antiproliferative, antimicrobial, and immunomodulatory activities. It has been shown that the IFNs and superantigens have an important effect on the course of certain autoimmune disorders, and thus we have examined the effect of the type I and type II IFNs on superantigen-induced stimulation. The type I IFNs, alpha, beta, and tau, inhibited induction of T cell proliferation by several staphylococcal enterotoxin superantigens; the type II IFN, gamma, was without effect. The type I IFNs inhibited T cell proliferation to the same extent, approximately 50% at 10(3) units of IFN/ml, and in a dose-dependent manner. Consistent with inhibition of proliferation, the type I IFNs also inhibited IL-2 production as well as levels of IL-2 receptor expression. Inhibition was not increased by using the IFNs in combination, suggesting that they inhibited proliferation by the same mechanism. IFNs alpha and beta, but not IFN-tau, were toxic to cells at high concentrations (> or = 10(4) units/ml). Thus, the mechanism by which type I IFNs inhibit cell proliferation differs from that associated with their toxic effects. A partial reduction of V beta-specific superantigen-induced T cell expansion by type I IFNs was also demonstrated using flow cytometry. We recently showed that superantigens play an important role in the reactivation of experimental allergic encephalomyelitis. The potent antiproliferative activities of the type I IFNs strongly suggest the further study of their use as therapies for superantigen-associated diseases, such as multiple sclerosis and other autoimmune disorders, as well as toxic shock syndrome.
J Interferon Cytokine Res 1995 Jan
PMID:Type I interferon inhibition of superantigen stimulation: implications for treatment of superantigen-associated disease. 764 33

Cytokine production by T cells in the cerebrospinal fluid (CSF) and central nervous system (CNS) of SJL/J mice during myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) was examined. Reverse transcriptase/polymerase chain reaction (RT/PCR) was used to measure interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) mRNA levels from perfused CNS tissue (brain and spinal cord) and from cells isolated from CSF. Animals were grouped according to EAE severity, ranging from asymptomatic (adjuvant only) to severe disease (paralysis or severe paresis). Cytokine signals, normalized to actin, were almost undetectable in control tissues, and only slightly elevated in whole CNS tissue from animals with mild EAE. Both cytokine messages were strongly upregulated in CNS tissues derived from severely affected animals, consistent with previous observations correlating disease progression with infiltration by memory/effector CD4+ T cells, the major source of these cytokines. This cytokine upregulation was specific to the CNS, since other organs from the same animals did not express significant levels of IL-2 and IFN-gamma. CSF was obtained from the cisterna magna of unperfused mice and verified as such by absence of red blood cells (RBCs) and by immunoglobulin concentration orders of magnitude lower than in serum. Cytokine message was measured in RNA isolated from cells in CSF. Levels of IL-2 and IFN-gamma mRNA in CSF cells were significantly elevated in mild EAE and strongly upregulated in severe disease, correlating with those in total CNS tissue. These results confirm the CSF as representative of the immune status of the CNS and indicate a role for IL-2 and IFN-gamma in inflammatory CNS disease.
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PMID:Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice. 829 48

The effect of orally administered type 1 interferons on the severity of acute experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease, was examined by inoculation of Lewis rats with guinea pig myelin basic protein (GPMBP) and complete Freund's adjuvant. Rats were fed either rat species-specific or human recombinant type 1 interferon (IFN) or mock IFN daily for 7 days preceding immunization and for 21 days thereafter. There was a significant decrease in the clinical score and inflammatory foci in animals fed 5000 units IFN compared with mock-treated animals. There was a significant decrease in clinical score and number of inflammatory foci in spinal cord in animals fed orally 5000 units human recombinant IFN-alpha PO compared with SC 5000 units recombinant human IFN-alpha. Oral administration of type 1 interferon, as opposed to subcutaneous administration, inhibited the secretion of IFN-gamma from ConA-activated draining popliteal lymph node cells compared with mock-fed animals. These experiments demonstrate that acute EAE is more effectively inhibited by equivalent amounts of orally in contrast to parenterally administered IFN-alpha. These results suggest that type 1 IFNs are active by the oral route and have significant clinical and histologic effects in acute autoimmune disease.
J Interferon Cytokine Res 1995 Feb
PMID:Modification of acute experimental autoimmune encephalomyelitis in the Lewis rat by oral administration of type 1 interferons. 859 Mar 14

Constitutive expression of the cellular proto-oncogenes c-fos and c-jun, and in a lesser extent ras, was demonstrated in the glioma cell line C-6 by flow cytometry analysis using specific mono and polyclonal antibodies. Basal expression of the products of the early response genes c-fos and c-jun were increased 66 and 50% when Theiler's murine encephalomyelitis virus (TMEV) infected these cells. No increase in ras transcription could be demonstrated after infection. This activation follows a kinetic reaching maximum values after 60 min and was proportional to the multiplicity of infection used. The described effect was completely abrogated by rabbit antibodies to TMEV but was not altered by normal rabbit serum. Furthermore, an intact infectious virion is needed to detect this effect. Fetal calf serum and lipopolysaccharide stimulation slightly increases c-fos and c-jun expression following a slower kinetics. Cytokine treatment (IL-1 alpha, IL-6, IFN-gamma and TNF alpha), did not induce oncogene over-expression. Therefore, this stimulation seems to be linked to the TMEV infectious process.
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PMID:Overexpression of basal c-fos and c-jun but not of ras oncogenes after Theiler's murine encephalomyelitis virus infection of glial cells. 879 9

For a series of immunological diseases including asthma, inflammatory arthritis and experimental allergic encephalomyelitis the non-classical major histocompatibility complex (MHC) genetics of man and mouse has been making rapid progress. Information is available not only for the disease associations of individual candidate genes but also from the first genome scans. In both species the proinflammatory cytokine genes and/or their related receptors and inhibitors (IL-1, IL-1r, IL-1ra, IL-2, IL-6r, TNF-alpha), and to a lesser extent the anti-inflammatory cytokine IL-4 are implicated as candidate control elements. In contrast, genes for the signalling and adhesion CD molecules have so far been inconspicuous. Most of the polymorphisms so far detected have been in the regulatory sequences of these genes, rather than in the exons. It is suggested that the benefit conferred on an individual by greater flexibility in its immunoregulatory machinery may be responsible for maintaining this form of polymorphism.
Cytokine 1996 Aug
PMID:Non-classical-MHC genetics of immunological disease in man and mouse. The key role of pro-inflammatory cytokine genes. 889 33

Aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase, prevented the clinical development of experimental autoimmune encephalomyelitis (EAE) with a reduction in inflammation and demyelination. Administration of AG reduced the expression of nitrosotyrosine in inflammatory lesions in the central nervous system. Cytokine expression, determined by semiquantitative PCR, revealed increased expression of IFN-gamma, IL-10, and TGF-beta, which was associated with protection from EAE, and reduced TNF-alpha, associated with the development of EAE. Furthermore, AG blocked the secretion of nitric oxide, TNF-alpha, and PGE2 in astrocyte cultures. AG did not influence the proliferation response of T cells to a pathogenic epitope of myelin basic protein. Down-regulation of nitric oxide by AG has widespread consequences for cytokine production in central nervous system inflammation and prevents EAE.
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PMID:Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis. 905 33

This study explores nasal administration of myelin basic protein (MBP) as a potential means of inducing tolerance to relapsing experimental autoimmune encephalomyelitis (PR-EAE), an experimental multiple sclerosis (MS) model that was induced in DA rats by immunization with rat spinal cord homogenate and incomplete Freund's adjuvant. DA rats received a total dosage of 0, 6, 60, 600 micrograms/rat of bovine MBP on ten consecutive days prior to immunization. EAE with typical course was observed in control rats receiving only PBS nasally, and in rats receiving 6 micrograms/rat of MBP. Rats receiving 60 micrograms/rat of MBP developed acute EAE but no relapse during 60 days of observation post immunization (p.i.). Only one of eight rats receiving 600 micrograms/rat of MBP developed slight, transient EAE. This protection was confirmed at the histology level and was associated with decreased levels of MBP-reactive IFN-gamma secreting Th1-like spleen cells on day 13 and 60 p.i. Rats receiving 60 and 600 micrograms/rat of MBP showed decreased serum anti-MBP IgG2b antibody levels on day 60 p.i., and rats receiving 600 micrograms/rat of MBP had marginally increased anti-MBP IgG1 antibody levels in serum compared to control EAE rats. Cytokine mRNA profiles in central nervous system (CNS) and spleen mononuclear cells were evaluated. Dose-dependent reduction of TNF-alpha mRNA expression were observed both in CNS and in splenocytes. Increased IL-4 and TGF-beta mRNA expression were observed in CNS of low (6 micrograms/rat) and median (60 micrograms/rat) dose of MBP tolerized rats and in splenocytes of rats tolerized with 600 micrograms/rat of MBP. We conclude that nasal administration of MBP in DA rat prevents EAE induced by immunization with whole rat spinal cord homogenate that, besides MBP, contains multiple antigenic myelin proteins. A mechanism involving MBP-reactive regulatory cells expressing IL-4 and TGF-beta mRNA acts as part in the induction of this tolerance.
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PMID:Nasal administration of myelin basic protein prevents relapsing experimental autoimmune encephalomyelitis in DA rats by activating regulatory cells expressing IL-4 and TGF-beta mRNA. 941 60

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS). We previously reported upregulation of gene expression for a number of proinflammatory cytokines, interleukin-1beta (IL-1beta), IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, and interferon-gamma (IFN-gamma), in the CNS of mice with myelin basic protein (MBP)-induced relapsing EAE by using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). However, in these mice there was no significant increase of gene expression for immunoregulatory cytokines (IL-4, IL-10, transforming growth factor-beta [TGF-beta]). We report here that gene expression for both proinflammatory and immunoregulatory cytokines increased during the course of disease in the CNS of mice with myelin oligodendrocyte glycoprotein (MOG)-induced nonrelapsing EAE. These results indicate that the gene expression pattern of immunoregulatory cytokines in the CNS may be different between MBP-induced and MOG-induced EAE and that it may influence the type of disease. Accordingly, the course of the disease may be influenced by the interplay between the proinflammatory and immunoregulatory cytokines.
J Interferon Cytokine Res 1998 Jun
PMID:The development of autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein is associated with an upregulation of both proinflammatory and immunoregulatory cytokines in the central nervous system. 966 Feb 49


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