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)

Lymphocytes from lymph nodes of Lewis rats with acute experimental allergic encephalomyelitis (EAE) contain high amounts of acid and neutral proteinases which hydrolyze myelin basic protein. The activity at neutral pH is also expressed by whole lymphocytes in isotonic medium, with about 50% more activity released by homogenization. Neutral proteinase activity in lymphocytes increases with the onset of acute EAE while the activity of those from Freund's adjuvant-injected controls increases somewhat later. The total neutral proteinase activity appears to be membrane-bound, most likely in the lysosomes, but half the total was associated with the nuclear fraction. The basic protein proteinase was compared with an enzyme described earlier, especially active toward polylysine, and some differences were noted. It appears that two enzymes may be present in lymphocytes which hydrolyze basic protein at a neutral pH. An increase in neutral proteinase activity was observed in some, but not all, lymphocyte preparations from patients in various stages of multiple sclerosis. The finding that whole activated lymphocytes are capable of hydrolyzing basic protein suggests that these cells which are believed to be precursors of mononuclear cells migrating into the central nervous system may be active agents in the early stages of myelin dissolution in experimental allergic encephalomyelitis. At present, such a mechanism is only theoretical, and the possibility that activated lymphocytes may be a factor in demyelination in multiple sclerosis is even more speculative.
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PMID:Baisc protein hydrolysis in lymphocytes of Lewis rats with experimental allergic encephalomyelitis. 8 Sep 45

Since calcium activated neutral proteinase (calpain) is present in the central nervous system (CNS) and degrades myelin proteins, this endopeptidase has been suggested to play a role in myelin destruction in demyelinating diseases such as multiple sclerosis (MS). In the present study, calpain immunocytochemical expression was examined in Lewis rats with acute experimental allergic encephalomyelitis (EAE), an animal model for MS and optic neuritis. To identify cells expressing calpain, we labeled rat optic nerve sections for calpain with a polyclonal myelin calpain antibody and with monoclonal antibodies for glial (GFAP, OX42) and inflammatory (CD2, ED2, ED1, IFN-gamma) cell-specific markers. The results showed increased calpain expression in microglia (OX42) and infiltrating macrophages (ED1,2) in EAE compared to normal controls. Astrocytes constitutively expressed calpain in controls and acute EAE. Reactive astrocytes in EAE located in or near inflammatory foci, exhibited markedly increased calpain expression. Most T cells in acute EAE showed low level calpain expression while activated IFN-gamma-producing lymphocytes in inflammatory foci exhibited elevated levels of calpain expression. Thus, our results demonstrate increased calpain expression (at transcriptional and/or translational levels) in a rat model of optic neuritis. A role for calpain in myelin destruction during optic neuritis may be relevant to the pathogenesis of this disorder.
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PMID:Increased calpain expression in experimental demyelinating optic neuritis: an immunocytochemical study. 951 58

In demyelinating diseases such as multiple sclerosis (MS), myelin membrane structure is destabilized as myelin proteins are lost. Calcium-activated neutral proteinase (calpain) is believed to participate in myelin protein degradation because known calpain substrates [myelin basic protein (MBP); myelin-associated glycoprotein] are degraded in this disease. In exploring the role of calpain in demyelinating diseases, we examined calpain expression in Lewis rats with acute experimental allergic encephalomyelitis (EAE), an animal model for MS. Using double-immunofluorescence labeling to identify cells expressing calpain, we labeled rat spinal cord sections for calpain with a polyclonal millicalpain antibody and with mAbs for glial (GFAP, OX42, GalC) and inflammatory (CD2, ED2, interferon gamma) cell-specific markers. Calpain expression was increased in activated microglia (OX42) and infiltrating macrophages (ED2) compared with controls. Oligodendrocytes (galactocerebroside) and astrocytes (GFAP) had constitutive calpain expression in normal spinal cords whereas reactive astrocytes in spinal cords from animals with EAE exhibited markedly increased calpain levels compared with astrocytes in adjuvant controls. Oligodendrocytes in spinal cords from rats with EAE expressed increased calpain levels in some areas, but overall the increases in calpain expression were small. Most T cells in grade 4 EAE expressed low levels of calpain, but interferon gamma-positive cells demonstrated markedly increased calpain expression. These findings suggest that increased levels of calpain in activated glial and inflammatory cells in EAE may contribute to myelin destruction in demyelinating diseases such as MS.
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PMID:Increased calpain expression in activated glial and inflammatory cells in experimental allergic encephalomyelitis. 957 59

Since myelin proteins are degraded in autoimmune demyelinating diseases such as optic neuritis, proteinases are believed to participate in myelinolysis. Calpain (calcium activated neutral proteinase) degrades myelin proteins at physiological pH and is found in glial and inflammatory cells involved in demyelination. To examine the putative role of calpain in myelinolysis, the activity and expression (translational and transcriptional) of this enzyme and endogenous inhibitor, calpastatin were examined in optic nerves of Lewis rats with experimental allergic encephalomyelitis (EAE), an animal model of optic neuritis. Calpain activity was examined via Western blotting by measuring the extent of myelin protein degradation and calpain-specific fodrin proteolysis in optic nerves from controls versus rats with experimental optic neuritis. RT-PCR studies demonstrated no significant change in millicalpain, microcalpain, or calpastatin expression at the mRNA level in optic nerves from animals with experimental optic neuritis compared to controls. However, myelin associated glycoprotein (MAG) levels were decreased by 25.5% while calpain translational expression and calpain-autolyzed fodrin levels were increased by 72.1% and 462.8% respectively, in experimental optic neuritis compared to controls. Translational expression of calpastatin isoforms (80, 68 and 55 KD) was not significantly different in rats with experimental optic neuritis compared to controls. Thus, increased activity and translational expression of calpain in experimental optic neuritis suggests this proteinase may participate in the degradation of myelin and cytoskeletal proteins in demyelinating diseases such as optic neuritis.
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PMID:Putative role of calpain in the pathophysiology of experimental optic neuritis. 982 Jul 87

Calcium-activated neutral proteinase (calpain) has been extensively studied over the past three decades such that many enzymatic and structural properties of this enzyme are well understood. However, the pathophysiological roles of calpain remain poorly defined. In addition to recent studies delineating a role for calpain in various pathological conditions, this proteinase has been implicated in the degradation of myelin proteins in autoimmune demyelinating diseases such as multiple sclerosis and experimental allergic encephalomyelitis (EAE). In EAE, calpain translational expression is significantly increased in activated glial/inflammatory cells that participate in myelinolysis while calpain substrates (axonal and myelin proteins) are lost. Thus, since all major myelin proteins are calpain substrates, early studies suggest calpain may play an important role in demyelination of the central nervous system.
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PMID:Pathophysiological role of calpain in experimental demyelination. 1008 76

EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E-restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG). These T cells drive the EAE pathogenesis to irreversible neurologic deficit. The aim of this study was to determine why LCV infection is important for this pathogenic role of B cells. Transcriptome comparison of LCV-infected B cells and CD20(+) spleen cells from rhesus monkeys shows increased expression of genes encoding elements of the Ag cross-presentation machinery (i.e., of proteasome maturation protein and immunoproteasome subunits) and enhanced expression of MHC-E and of costimulatory molecules (CD70 and CD80, but not CD86). It was also shown that altered expression of endolysosomal proteases (cathepsins) mitigates the fast endolysosomal degradation of the MOG40-48 core epitope. Finally, LCV infection also induced expression of LC3-II(+) cytosolic structures resembling autophagosomes, which seem to form an intracellular compartment where the MOG40-48 epitope is protected against proteolytic degradation by the endolysosomal serine protease cathepsin G. In conclusion, LCV infection induces a variety of changes in B cells that underlies the conversion of destructive processing of the immunodominant MOG40-48 epitope into productive processing and cross-presentation to strongly autoaggressive CTLs.
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PMID:Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein. 2741 14

The efficacy of B cell depletion therapy in multiple sclerosis indicates their central pathogenic role in disease pathogenesis. The B lymphotropic EBV is a major risk factor in multiple sclerosis, via as yet unclear mechanisms. We reported in a nonhuman primate experimental autoimmune encephalomyelitis model that an EBV-related lymphocryptovirus enables B cells to protect a proteolysis-sensitive immunodominant myelin oligodendrocyte glycoprotein (MOG) epitope (residues 40-48) against destructive processing. This facilitates its cross-presentation to autoaggressive cytotoxic MHC-E-restricted CD8+CD56+ T cells. The present study extends these observations to intact human B cells and identifies a key role of autophagy. EBV infection upregulated APC-related markers on B cells and activated the cross-presentation machinery. Although human MOG protein was degraded less in EBV-infected than in uninfected B cells, induction of cathepsin G activity by EBV led to total degradation of the immunodominant peptides MOG35-55 and MOG1-20 Inhibition of cathepsin G or citrullination of the arginine residue within an LC3-interacting region motif of immunodominant MOG peptides abrogated their degradation. Internalized MOG colocalized with autophagosomes, which can protect from destructive processing. In conclusion, EBV infection switches MOG processing in B cells from destructive to productive and facilitates cross-presentation of disease-relevant epitopes to CD8+ T cells.
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PMID:EBV Infection Empowers Human B Cells for Autoimmunity: Role of Autophagy and Relevance to Multiple Sclerosis. 2859 28