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)

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) by cells in the central nervous system (CNS) of Lewis rats during acute experimental allergic encephalomyelitis (EAE). A few endothelial cells in the CNS of normal rats expressed ICAM-1, whereas during the active phase of EAE, ICAM-1 was present on many endothelial cells. This alteration was detectable the day before clinical symptoms. Since histopathological studies showed few detectable mononuclear cells or inflammatory foci in any section of the preclinical rats, the expression of ICMA-1 was considered to be important at least in the early stage of inflammation. LFA-1 was seen on perivascular infiltrating cells. An increase in either ICAM-1- or LFA-1-positive cells was initially seen in the lumbosacral portion of the spinal cord, which then extended to the thoracic portion. The number of either ICAM-1- or LFA-1-positive cells peaked on the day of clinical onset in the lumbosacral portion. In contrast, in the thoracic portion, a peak in the number of either ICAM-1- or LFA-1-positive cells was observed on the day after clinical onset. This ascending extension of either ICAM-1- or LFA-1-positive cells was correlated with the progression of neurologic signs. It is suggested that increased expression of ICAM-1 and LFA-1 in the CNS of rat EAE may promote the extravasation of lymphocytes across the blood-brain barrier and be related to progression of the disease.
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PMID:Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in the spinal cord of rats during acute experimental allergic encephalomyelitis. 774 38

Based on previous observations showing that inflammatory episodes in the central nervous system (CNS) of SJL/J mice with adoptively transferred experimental allergic encephalomyelitis (EAE) are associated with a concomitant upregulation of adhesion-related molecules around CNS blood vessels, the present study was undertaken to block the development of EAE with injections of monoclonal antibodies (mAbs) to two different adhesion molecules. The mAbs selected were directed against intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) and were administered at different doses (50 micrograms-1 mg), as single and multiple injections, and at various time points post-transfer of myelin basic protein-specific lymphocytes. Although one group of EAE mice given alpha LFA-1 displayed adverse effects after treatment, on the whole, neither mAb had a statistically significant effect on the outcome of EAE in this murine model. There was, however, down-regulation in the CNS of the respective adhesion molecules after treatment. Whether the lack of beneficial effect was related to the stage of EAE at which the mAbs were administered, remains to be proven. This is the first report suggesting that alpha ICAM-1 and alpha LFA-1 mAbs might have opposite effects (i.e. ameliorating or worsening) upon murine EAE and the different effect of alpha LFA-1 might be related to this molecule being involved in more cell signalling mechanisms than ICAM-1.
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PMID:Anti-adhesion molecule therapy in experimental autoimmune encephalomyelitis. 810 61

Activation of the vascular endothelium is important in the development of inflammation. Activated endothelial cells (EC) express surface markers not expressed by quiescent EC. These surface markers augment adhesion reactions and leukocyte migration. We examined microvessel EC activation longitudinally in experimental autoimmune encephalomyelitis (EAE) in Lewis rats. CNS microvessels were isolated at 0, 3, 7, 12, 20, and 30 days post-inoculation (PI). Normal and CFA-injected rat microvessels do not express activation antigens (Ag). Increased expression of major histocompatibility complex (MHC) class II molecule and intercellular adhesion molecule-1 (ICAM-1) were detected on CNS microvessels from immunized rats at 7 days PI, prior to development of clinical signs, and at 12 days PI. Enhanced MHC class I molecule was seen only at 12 days. MHC class II molecule expression was focally expressed along microvessel fragments. By 20 days PI, EC did not exhibit increased levels of any of the markers tested. Perivascular cells (possibly pericytes), however, were found to express MHC class II molecule and ICAM-1 up to 30 days PI. During the recovery phase isolated CNS microvessels from MBP-immunized rats were unresponsive to IFN gamma-mediated endothelial activation. Unresponsiveness was independent of IFN gamma concentration. These results suggest that the endothelium is restored to functional quiescence during the recovery phase of acute EAE.
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PMID:Recovery phase of acute experimental autoimmune encephalomyelitis in rats corresponds to development of endothelial cell unresponsiveness to interferon gamma activation. 872 61

Regulatory T cells recognizing TCR determinants presumably play a critical role in the control of experimental autoimmune encephalomyelitis, a prototype tissue-specific autoimmune disease. This study was initiated to determine whether regulatory T cells can be induced against a V beta 17a CDR2 peptide (residues 50-68) in SJL/J mice. Although the TCR peptide showed regulatory effects in vivo, the presence of T cells specific for the peptide could not be proven with conventional proliferation assays. Unexpectedly, in the presence of myelin basic protein-specific T clone cells (Tcc), the sensitized spleen cells vigorously proliferated in response to the TCR peptide. The subsequent experiment showed that this was due to the outstanding capability of the Tcc as APC for the exogenous TCR peptide. Using the Tcc as APC, we were able to establish V beta 17a50-68-specific T cell lines from in vivo primed spleen cells. The line cells were MHC class I restricted and dominated by T cells with a distinct surface phenotype (CD4-CD8-V beta 17a+). Presentation of the peptide by the Tcc was inhibited by treatment with gelonin that could block a MHC class I presentation pathway. The ability of T cells to present the TCR peptide was not related to their Ag specificity, but correlated with the expression levels of MHC class I molecules and adhesion molecules such as intercellular adhesion molecule-1 and B7-1 on their surface. The TCR peptide-specific T cells produced a soluble mediator(s) that is inhibitory for T cell activation and were protective against actively induced experimental autoimmune encephalomyelitis. These results show that V beta 17a50-68 vaccination induces regulatory CD4-CD8- T cells that could interact with T cells presenting relevant TCR fragments.
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PMID:T-T cellular interaction between CD4-CD8- regulatory T cells and T cell clones presenting TCR peptide. Its implication for TCR vaccination against experimental autoimmune encephalomyelitis. 875 68

Experimental allergic encephalomyelitis (EAE) is facilitated in resistant BALB/c mice by intraperitoneal infection with an avirulent Semliki Forest virus (SFV-A7). Viral infection increases the incidence of EAE from 15-30% to 60-90% and speeds up appearance of paralysis from 24 to 14 days. In this paper, we describe treatment of virus-facilitated EAE with monoclonal antibodies (mAbs) against leukocyte and/or endothelial cell adhesion molecules. Therapy with mAb against ICAM-1 (intercellular adhesion molecule-1) had a modest effect, but caused hemorrhagic brain and spinal cord lesions. Therapy with mAb against Mac-1 (alpha M beta 2-integrin) was well tolerated but had no effect. Therapy with mAb against VLA-4 (alpha 4 beta 1-integrin) was safe, diminished both clinical and histopathological signs of EAE, decreased induction of VCAM-1 (vascular cell adhesion molecule-1) on brain vessels and diminished infiltration of VLA-4+ cells into the brain. The amount of viral antigen in the brain was not altered. We conclude that facilitation of leukocyte entry into the brain is a major mechanism for viral facilitation of EAE in the BALB/c mouse, and that facilitation can be inhibited by anti-adhesion therapy. This may have implications for treatment of relapses triggered by viral infections in multiple sclerosis.
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PMID:Therapy with antibody against leukocyte integrin VLA-4 (CD49d) is effective and safe in virus-facilitated experimental allergic encephalomyelitis. 900 49

During inflammation, T cells transmigrate from the bloodstream into perivascular tissues. As T cells transmigrate, they undergo a series of attachments to and detachments from the endothelium and then extravasate into the extracellular matrix (ECM). T cell migration into the ECM involves a number of mechanisms that influence cell-ECM interactions. The modulation of integrin expression and affinity are two such mechanisms in which cells can alter their ability to interact with other cells and ECM. We show in vitro that transmigrated T cells exhibit down-regulation of very late activation antigen-4 and leukocyte function-associated antigen-1 integrin surface expression and a decrease in binding to recombinant vascular cell adhesion molecule-1 and recombinant intercellular adhesion molecule-1. Also, transmigrated T cells displayed an increase in binding to collagens I and IV and fibronectin. Further, brain sections of experimental autoimmune encephalomyelitis mice demonstrated that as T cells migrated farther into the tissue, very late activation antigen-4 expression was lost while CD4 expression remained unchanged. The significance of these findings in the modulation of the inflammatory response is discussed.
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PMID:T cell adhesion to endothelial cells and extracellular matrix is modulated upon transendothelial cell migration. 901 Apr 46

The functional expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and MAdCAM-1 in the choroid plexus is indicative of a role of this structure in the communication of the immune system with the central nervous system (CNS). In order to gain further insight into the possible functions of adhesion molecules expressed in the choroid plexus, we investigated the exact ultrastructural localization of VCAM-1, ICAM-1 and MAdCAM-1 on semithin and ultrathin cryosections of the choroid plexus of healthy mice and of mice suffering from experimental autoimmune encephalomyelitis (EAE). In the healthy choroid plexus VCAM-1 and ICAM-1, but not MAdCAM-1, could be detected on the apical surface of the choroid plexus epithelial cells. During EAE, immunoreactivity for VCAM-1 and ICAM-1 was dramatically increased. Additionally, apical expression of MAdCAM-1 was observed on individual choroid plexus epithelial cells during EAE. At the same time, VCAM-1, ICAM-1 or MAdCAM-1 were never present on the endothelial cells of the fenestrated capillaries within the choroid plexus. The polar expression of VCAM-1, ICAM-1 and MAdCAM-1 on the apical surface of choroid plexus epithelial cells, which form the blood-cerebrospinal fluid barrier, implies a previously unappreciated function of this barrier in the immunosurveillance of the CNS.
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PMID:Ultrastructural localization of adhesion molecules in the healthy and inflamed choroid plexus of the mouse. 1038 70

Interleukin-6 (IL-6) plays an important role in the regulation of the inflammatory response in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous reports indicated that a variable number tandem repeat (vntr) polymorphism in the 3'flanking region of the IL-6 gene (C allele) is associated with altered activity of IL-6 in vivo. Therefore, we analyzed the frequency distribution of IL-6 gene C allele vntr poymorphism in 96 MS patients and 106 ethnically matched healthy controls. Moreover, possible correlations between genotypic differences of IL-6 gene and serum levels of IL-6, soluble IL-6 receptor (sIL6-R), soluble gp130 (sgp130), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were investigated. There were no differences in the allelic distribution of the IL-6 gene C allele between MS patients and healthy controls, and no association of the IL-6 gene C allele with serum levels of IL-6, sIL-6R, spg130, sICAM and sVCAM-1 was found.
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PMID:No association of serum levels of interleukin-6 and its soluble receptor components with a genetic variation in the 3'flanking region of the interleukin-6 gene in patients with multiple sclerosis. 1107 34

A role for alpha4 and beta7 integrins in mediating leucocyte entry into the central nervous system in the multiple sclerosis (MS)-like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated. However, the individual contributions of their respective ligands mucosal addressin cell adhesion molecule-1 (MAdCAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-cadherin expressed on the blood-brain barrier has not been determined. In the present paper, it is shown that an antibody directed against MAdCAM-1, the preferential ligand for alpha4beta7, effectively prevented the development of a progressive, non-remitting, form of EAE, actively induced by injection of myelin oligodendrocyte glycoprotein peptide (MOG(35-55)) autoantigen. Combinational treatment with both anti-MAdCAM-1, VCAM-1, and intercellular adhesion molecule-1 (ICAM-1) (ligand for integrin lymphocyte function-associated antigen (LFA)-1) mAbs led to more rapid remission than that obtained with anti-MAdCAM-1 antibody alone. However, neither MAdCAM-1 monotherapy, nor combinational antibody blockade was preventative when administered late in the course of disease progression. In conclusion, MAdCAM-1 plays a major contributory role in the progression of chronic EAE and is a potential therapeutic target for the treatment of MS. Critically, antivascular addressin therapy must be given early in the course of disease prior to the establishment of irreversible damage if it is to be effective, as a single treatment modality.
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PMID:Prevention of a chronic progressive form of experimental autoimmune encephalomyelitis by an antibody against mucosal addressin cell adhesion molecule-1, given early in the course of disease progression. 1111 75

In experimental autoimmune encephalomyelitis (EAE), Th1 cells are responsible for disease induction while Th2 cells can be protective. To address the mechanisms of this differential behavior, we utilized organotypic murine entorhinal-hippocampal slice cultures to analyze interactions between myelin basic protein-specific Th1 and Th2 cells with microglial cells. While both Th1 and Th2 cells induced CD40 expression, only Th1 cells induced intercellular adhesion molecule-1 (ICAM-1) expression on microglia. Moreover, Th2 cells prevented or even reversed Th1-induced ICAM-1 upregulation. Evidently, Th2 cells could diminish Th1-induced inflammatory reactions and actively support the resting state of microglia, which could be one mechanism of Th2-mediated remission of neuroinflammation during EAE.
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PMID:Th2 cells support intrinsic anti-inflammatory properties of the brain. 1152 2


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