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)

Intracerebral inoculation of mice with Theiler's murine encephalomyelitis virus results in an intense inflammatory response of mononuclear leukocytes which infiltrate into the central nervous system. Resistant strains of mice have the ability to clear virus whereas susceptible strains become infected persistently and are associated with chronic demyelination which is proposed to be immune-mediated. In an attempt to better understand the role of the immune response during demyelination, mononuclear leukocytes were isolated from the central nervous system of infected mice and stained by an immunoperoxidase technique with anti-Thy-1.2, anti-L3T4, anti-Lyt-2 and anti-MAC-1 mAb. Infection of susceptible SJL/J mice resulted in a biphasic immune response which peaked on days 7 and 27 post-infection. In contrast, a single peak (day 7) was observed in resistant C57BL/10SNJ mice. The presence of Thy-1.2, L3T4, and MAC-1+ cells was similar between the two strains. However, although the number of Lyt-2+ cells peaked on day 7 in C57BL/10SNJ mice, they were not detected in SJL/J mice until 14 days post-infection and gradually increased in number over the course of infection. To further study the role of T cells in demyelination, serial frozen sections of brain and spinal cord were stained for the presence of Lyt-2 and L3T4+ cells in the lesions of chronically infected SJL/J mice. L3T4+ cells were observed predominantly in perivascular regions while Lyt-2+ cells were observed infiltrating the parenchyma. These results provide further evidence that Lyt-2+ lymphocytes are important in the mechanism of susceptibility/resistance to Theiler's murine encephalomyelitis virus-induced demyelination.
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PMID:Characterization of the inflammatory response in the central nervous system of mice susceptible or resistant to demyelination by Theiler's virus. 249 23

Migration of cells into the central nervous system (CNS) is a pivotal step in the pathogenesis of immune-mediated diseases such as multiple sclerosis (MS), experimental allergic encephalomyelitis (EAE) and virus-induced demyelinating diseases. Such migration is dependent on expression of adhesion molecules. The expression of adhesion molecules in the CNS was studied in Biozzi ABH mice infected with Semliki Forest virus (SFV) A7(74) - an important demyelinating model of MS. Expression of LFA-1alpha/CD11a, LFA-1beta/CD18 and ICAM-1/CD56 were rapidly elevated and remained high whereas MAC-1, CD44 and VCAM-1/CD106 were less widely expressed. The alpha4-integrin VLA-4/CD49d was more specifically associated with CNS lesions. To identify the importance of VLA-4, CD44, ICAM-1 and MAC-1 in the pathogenesis of SFV infection, monoclonal antibodies that block these adhesion molecules were administered in vivo during infection. Anti-VLA-4 treatment dramatically reduced the cellular infiltrates and demyelination within the CNS but did not affect the clearance of virus while antibodies to CD44, ICAM and MAC-1 antibody treatment had no effect. This study demonstrates that SFV infection induces the expression of adhesion molecules within the CNS and that VLA-4 plays an important role in the development of inflammation and demyelination in the CNS following SFV infection.
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PMID:A role for alpha4-integrin in the pathology following Semliki Forest virus infection. 1081 83

The removal of damaged myelin is central to repair after injury to axons and in autoimmune demyelinating diseases. Complement receptor 3 (CR3/MAC-1) plays a major role in mediating the phagocytosis of damaged myelin by macrophages and microglia. We studied the modulation (inhibition and augmentation) of CR3/MAC-1 mediated myelin phagocytosis by mAbs that bind to distinct epitopes of subunits alphaM and beta2 of CR3/MAC-1. mAb M1/70 anti-alpha(M) and mAb 5C6 anti-alpha(M) inhibited, whereas mAb M18/2 anti-beta2 augmented myelin phagocytosis. This mAb-induced modulation of myelin phagocytosis occurred in the presence and absence of active complement. Inhibition induced by M1/70 or 5C6 did not add when the two were combined. Combining M1/70 or 5C6 with M18/2 reduced the augmentation induced by M18/2 alone. CR3/MAC-1-mediated myelin phagocytosis may thus be subjected to modulation between efficient and inefficient functional/activation states. These observations and conclusions may offer an explanation for the observed discrepancy between efficient myelin phagocytosis in experimental allergic encephalomyelitis and inefficient myelin phagocytosis after injury to CNS axons, although in both instances macrophages/microglia express CR3/MAC-1.
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PMID:Modulation (inhibition and augmentation) of complement receptor-3-mediated myelin phagocytosis. 1144 57

Hormones can exert significant protective effects on autoimmune diseases by activating immunoregulatory mechanisms. One of the possible mechanisms of hormonal protection might be through the anti-inflammatory effects of the TGF-beta molecule. The present study investigated the changes in expression of two TGF-beta isoforms, TGF-beta1 and TGF-beta3, in C57BL/6 and TCR transgenic (T/R+) B10.PL mice that manifested or were protected against clinical signs of experimental autoimmune encephalomyelitis (EAE) with 17beta-estradiol (E2) treatment. We here demonstrate an inverse relationship between expression of TGF-beta1 that is enhanced in mice with EAE, and TGF-beta3 that is enhanced in E2-protected mice. The differential expression of TGF-beta isoforms was observed in spinal cord tissue but not spleen. Additionally TGF-beta1 expression was evident both in whole spinal cord tissue and mononuclear cells isolated from inflamed tissue, in contrast to TGF-beta3 that was only detected in spinal cord tissue but not in mononuclear cells. Further studies revealed that CD3 and especially MAC-1 positive cells were the main source of TGF-beta1 in the mononuclear CNS population. Of crucial importance, the TGF-beta3 isoform displayed anti-proliferative properties towards encephalitogenic cells in vitro. We propose that the TGF-beta1 and TGF-beta3 isoforms play opposing roles in the expression of EAE.
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PMID:Opposing roles for TGF-beta1 and TGF-beta3 isoforms in experimental autoimmune encephalomyelitis. 1469 59

Mac-1 (CD18/CD11b) is a member of the beta2-integrin family of adhesion molecules and is implicated in the development of many inflammatory diseases. The role of Mac-1 in the development of CNS demyelinating diseases, including multiple sclerosis, is not understood, and Ab inhibition studies in experimental allergic encephalomyelitis (EAE), the animal model for multiple sclerosis, have produced conflicting findings. To clarify these results and to determine Mac-1-mediated mechanisms in EAE, we performed EAE using Mac-1-deficient mice. Mac-1 homozygous-deficient, but not Mac-1 heterozygous-deficient mice, had significantly delayed onset and attenuated EAE. Leukocyte infiltration was similar in both groups of mice in early disease but significantly reduced in spinal cords of receptor-deficient mice in late disease. Adoptive transfer of Ag-restimulated T cells from wild-type to Mac-1-deficient mice produced significantly attenuated EAE, whereas transfer of Mac-1-deficient Ag-restimulated T cells to control mice failed to induce EAE. T cells from myelin oligodendrocyte glycoprotein (MOG)35-55 peptide-primed Mac-1-deficient mice displayed an altered cytokine phenotype with elevated levels of TGF-beta and IL-10, but reduced levels of IL-2, IFN-gamma, TNF-alpha, IL-12, and IL-4 compared with control mice. Mac-1-deficient T cells from primed mice proliferated comparably to that of control T cells on MOG35-55 restimulation in vitro. However, the draining lymph nodes of MAC-1-deficient mice on day 10 after MOG35-55 immunization contained lower frequency of blast T cells than in control mice, suggesting poor priming. Our results indicate that Mac-1 expression is critical on both phagocytic cells and T cells for the development of demyelinating disease.
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PMID:Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis. 1627 84