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 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

Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show here that, as in EAE, MT-I+II proteins were expressed in brain lesions of MS patients. Cells expressing MT-I+II were mainly astrocytes and activated monocytes/macrophages. Interestingly, the levels of MT-I+II were slightly increased in the inactive MS lesions in comparison with the active lesions, suggesting that MTs may be important in disease remission.
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PMID:Metallothionein expression in the central nervous system of multiple sclerosis patients. 1286 91