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)

Sxteen pure metals were implanted as pellets of powder or as wires into the brains of rats. Al, Be, Cr, Fe, Pb, Sn, and W were relatively innocuous. Mg and Mn produced local necrosis. Bi, Cd, Co, Cu and Ni produced more severe local necrosis. Viable tissue adjacent to Co and Ni necrotic lesions had some perivascular lymphocytic infiltrates. Zn implants caused very little necrosis but adjacent areas had prominent perivascular lymphocytic cuffs. The infiltrates persisted for at least 4 weeks but disappeared as soon as the zinc was removed. Some compounds of zinc were also capable of inducing infiltrates. The perivascular infiltrates resembled the lesions of allergic encephalomyelitis, but there was no correlation between the ability of metal powders to induce lymphocytic infiltrates after intracerebral implantation and their adjuvancy after intraperitoneal injection with neural antigen.
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PMID:Lymphocytic inflammation produced by intracerebral implantation of zinc and other metals. 69 Jun 68

In this study, we report initial results concerning the effects of elevated dietary trace metals upon delayed relapsing experimental allergic encephalomyelitis (EAE) in SJL mice. Animals were assigned to a control diet as well as to diets with increased content of NiS0(4) and ZnS0(4) prior to immunization for EAE. During a six month follow-up period, trends appeared which indicated that the incidence of EAE might be lower in the nickel-fed animals than in the comparison groups. EAE onset also seemed to occur later in the nickel group. Histopathologic ratings of standardized tissue sections suggested more widespread inflammatory disease of the central nervous system in the high zinc group.
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PMID:Effects of altered dietary trace metals upon experimental allergic encephalomyelitis. 228 50

The leader (L) peptide is located in the amino-terminal part of the polyprotein of members of the Cardiovirus (which includes Theiler's murine encephalomyelitis virus) and Aphthovirus genera of picornaviruses. Although the function of L is unknown, strain DA of Theiler's murine encephalomyelitis virus with a mutation of L produces a cell-specific restricted infection. We now report that the DA L peptide is a metalloprotein and that zinc binds to a Cys-His motif that is conserved among cardioviruses.
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PMID:The leader peptide of Theiler's murine encephalomyelitis virus is a zinc-binding protein. 749 25

Matrix metalloproteinases (MMPs) are a large family of Zn2+ endopeptidases that are expressed in inflammatory conditions and are capable of degrading connective tissue macromolecules. MMP-like enzymes are also involved in the processing of a variety of cell surface molecules including the pro-inflammatory cytokine TNF-alpha. MMPs and TNF-alpha have both been implicated in the pathology associated with neuro-inflammatory diseases (NIDs), particularly multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). We have shown that BB-1101, a broad spectrum hydroxamic acid-based combined inhibitor of MMP activity and TNF processing, reduces the clinical signs and weight loss in an acute EAE model in Lewis rats. However, little is known about which MMPs are involved in the neuroinflammatory process. In order to determine the optimum inhibitory profile for an MMP inhibitor in the treatment of NID, we investigated the profile of MMP expression and activity during EAE. The development of disease symptoms was associated with a 3-fold increase in MMP activity in the cerebrospinal fluid (CSF), which could be inhibited by treatment with BB-1101, and an increase in 92 kDa gelatinase activity detected by gelatin substrate zymography. Quantitative PCR analysis of normal and EAE spinal cord revealed the expression of at least seven MMPs. Of these, matrilysin showed the most significant change, being elevated over 500 fold with onset of clinical symptoms and peaking at maximum disease severity. Of the other six MMPs detected, 92 kDa gelatinase showed a modest 5 fold increase which peaked at the onset of clinical signs and then declined during the most severe phase of the disease. Matrilysin was localised by immunohistochemistry to the invading macrophages within the inflammatory lesions of the spinal cord. Matrilysin's potent broad spectrum proteolytic activity and its localisation to inflammatory lesions in the CNS suggest this enzyme could be particularly involved in the pathological processes associated with neuro-inflammatory disease.
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PMID:Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-alpha inhibitor. 911 83

Regulated expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) plays a role in various physiological processes. To determine in vivo how unbalanced expression of these factors can promote or affect the course of pathologies, we knocked out the mouse gelatinase B gene by replacing the catalytic and zinc-binding domains with an antisense-oriented neomycin resistance gene. Adult gelatinase B-deficient mice and wild-type controls could be induced to develop experimental autoimmune encephalomyelitis (EAE) with similar scores for neurologic disease, blood-brain barrier permeability, and central nervous system histopathology. However, whereas diseased control animals showed necrotizing tail lesions with hyperplasia of osteocartilaginous tissue, adult gelatinase B-deficient mice were resistant to this tail pathology. Gelatinase B-deficient mice younger than 4 weeks of age were significantly less susceptible to the development of EAE than were age matched controls and, even as they aged, they remained resistant to tail lesions. These data illustrate that gelatinase B expression plays a role in the development of the immune system and that, in ontogenesis, the propensity to develop autoimmunity is altered by the absence of this MMP.
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PMID:Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions. 1058 14

We examined the expression and roles of neuroprotective metallothionein-I+II (MT-I+II) in the rat CNS in experimental autoimmune encephalomyelitis (EAE), an animal model for the human autoimmune disease, multiple sclerosis (MS). EAE caused significant macrophage activation, T-lymphocyte infiltration, and astrogliosis in spinal cord, brain stem, and cerebellum, which peaked 14-18 days after immunization. The remission of symptoms and histopathological changes began at days 19-21 and were completed by days 30-40. MT-I+II expression was increased significantly in EAE infiltrates. In order to study the effects of increased MT levels, we administered Zn-MT-II intraperitoneally (i.p.) to rats during EAE. Clinically, Zn-MT-II treatment reduced the severity of EAE symptoms and mortality in a time- and dose-dependent manner. Histopathologically, Zn-MT-II increased reactive astrogliosis and decreased macrophages and T lymphocytes significantly in the CNS. In spleen sections, the number of macrophages both in control and EAE-sensitized rats was reduced by Zn-MT-II, while the number of lymphocytes remained unaltered by Zn-MT-II. Therefore, we suggest that MT-II has peripheral mechanisms of action on macrophages, while T lymphocytes are affected locally in the CNS. During EAE, oxidative stress was decreased by Zn-MT-II, which could contribute to the diminished clinical scores observed. None of the effects caused by Zn-MT-II could be attributable to the zinc content. These results suggest MT-I+II as potentially useful factors for the treatment of EAE/MS.
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PMID:Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis. 2923 98

Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human autoimmune disease multiple sclerosis (MS). Proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are considered important for induction and pathogenesis of EAE/MS disease, which is characterized by significant inflammation and neuroglial damage. We have recently shown that the exogenous administration of the antioxidant protein zinc-metallothionein-II (Zn-MT-II) significantly decreased the clinical symptoms, mortality, and leukocyte infiltration of the CNS during EAE. However, it is not known how EAE progression is regulated nor how cytokine production and cell death can be reduced. We herewith demonstrate that treatment with Zn-MT-II significantly decreased the CNS expression of IL-6 and TNF-alpha during EAE. Zn-MT-II treatment could also significantly reduce apoptotic cell death of neurons and oligodendrocytes during EAE, as judged by using TUNEL and immunoreactivity for cytochrome c and caspases 1 and 3. In contrast, the number of apoptotic lymphocytes and macrophages was less affected by Zn-MT-II treatment. The Zn-MT-II-induced decrease in proinflammatory cytokines and apoptosis during EAE could contribute to the reported diminution of clinical symptoms and mortality in EAE-immunized rats receiving Zn-MT-II treatment. Our results demonstrate that MT-II reduces the CNS expression of proinflammatory cytokines and the number of apoptotic neurons during EAE in vivo and that MT-II might be a potentially useful factor for treatment of EAE/MS.
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PMID:Metallothionein treatment reduces proinflammatory cytokines IL-6 and TNF-alpha and apoptotic cell death during experimental autoimmune encephalomyelitis (EAE). 1142 79

Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human demyelinating disease multiple sclerosis (MS). EAE and MS are characterized by significant inflammation, demyelination, neuroglial damage, and cell death. Metallothionein-I and -II (MT-I + II) are antiinflammatory and neuroprotective proteins that are expressed during EAE and MS. We have shown recently that exogenous administration of Zn-MT-II to Lewis rats with EAE significantly reduced clinical symptoms and the inflammatory response, oxidative stress, and apoptosis of the infiltrated central nervous system areas. We show for the first time that Zn-MT-II treatment during EAE significantly prevents demyelination and axonal damage and transection, and stimulates oligodendroglial regeneration from precursor cells, as well as the expression of the growth factors basic fibroblast growth factor (bFGF), transforming growth factor (TGF)beta, neurotrophin-3 (NT-3), NT-4/5, and nerve growth factor (NGF). These beneficial effects of Zn-MT-II treatment could not be attributable to its zinc content per se. The present results support further the use of Zn-MT-II as a safe and successful therapy for multiple sclerosis.
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PMID:Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis. 3088 17

Heme oxygenase-1 (HO-1, encoded by HMOX1) dampens inflammatory reactions via the catabolism of heme into CO, Fe, and biliverdin. We report that expression of HO-1 dictates the pathologic outcome of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Induction of EAE in Hmox1(-/- )C57BL/6 mice led to enhanced CNS demyelination, paralysis, and mortality, as compared with Hmox1(+/+) mice. Induction of HO-1 by cobalt protoporphyrin IX (CoPPIX) administration after EAE onset reversed paralysis in C57BL/6 and SJL/J mice and disease relapse in SJL/J mice. These effects were not observed using zinc protoporphyrin IX, which does not induce HO-1. CoPPIX protection was abrogated in Hmox1(-/-) C57BL/6 mice, indicating that CoPPIX acts via HO-1 to suppress EAE progression. The protective effect of HO-1 was associated with inhibition of MHC class II expression by APCs and inhibition of Th and CD8 T cell accumulation, proliferation, and effector function within the CNS. Exogenous CO mimicked these effects, suggesting that CO contributes to the protective action of HO-1. In conclusion, HO-1 or exposure to its end product CO counters autoimmune neuroinflammation and thus might be used therapeutically to treat MS.
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PMID:Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation. 1725 58

The DA strain and other members of the TO subgroup of Theiler's murine encephalomyelitis virus synthesize the L* protein from an alternative initiation codon. L* is considered to play a key role in viral persistence and demyelination in susceptible strains of mice, although this hypothesis is still controversial. By using a mutant virus that expresses FLAG epitope-tagged L*, it was demonstrated previously that L* is expressed exclusively in neurons in vivo in the acute phase of infection in the central nervous system (CNS). However, in the mutant virus, the C-H-C-C zinc-binding motif in the leader protein (L) was disrupted by the insertion of the FLAG epitope, resulting in clearance of the virus from the CNS. Therefore, a further two mutant viruses were newly generated, expressing FLAG epitope-tagged L* in which the C-H-C-C zinc-binding motif within L is spared. Both mutant viruses caused persistence and demyelination successfully in spinal cords and enabled us to identify L* immunohistochemically in the demyelinating lesions.
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PMID:Expression of L* protein of Theiler's murine encephalomyelitis virus in the chronic phase of infection. 1762 31


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