UMLS:C0014070 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0014070 (encephalomyelitis)
13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Juvenile strain-13 guinea pigs challenged with whole central nervous system (CNS) tissue in complete Freund's adjuvant (CFA) developed chronic-relapsing (CR) experimental allergic encephalomyelitis (EAE). The animals that recovered from the first clinical episode were divided into three groups. One group was left untreated, one group was treated with three intracardiac injections of 100 micrograms glutaraldehyde-fixed myelin basic protein (MBP)-liposomes (MBP-L-GA) given once a week, and one group was treated with cytochrome c-liposomes (CYC-L-GA). The animals treated with MBP-liposomes were very well protected against further relapses. In vitro proliferative responses of peripheral blood lymphocytes (PBL) were performed repeatedly on most animals. The lymphocytes exhibited excellent proliferative responses to MBP, proteolipid apoprotein (PLP) and whole myelin, as well as to purified protein derivative (PPD) and concanavalin-A (ConA). High proliferative responses were recorded over the entire period of observation which lasted 12-22 months, each time the animals were tested in remission or in full relapse. However, a sharp decrease in proliferative responses was observed in most animals when the assay was performed 24-48 h before to 24 h after entering a relapse. The results demonstrate the presence of long-term and sustained cell-mediated responses to two distinct neuroantigens, and show fluctuations of both neuroantigen-specific and nonspecific responses concordant with a well-defined phase of the disease. Isoelectric focusing and immunofixation was performed on sera and cerebrospinal fluids obtained at the time of sacrifice. The pattern showed clear oligoclonal IgG bands (OB) in the samples obtained from untreated, CYC-L-GA-treated as well as in the MBP-L-GA-treated animals.
...
PMID:Chronic-relapsing experimental allergic encephalomyelitis in strain-13 guinea pigs: cell-mediated immunity and IgG isoelectric focusing in myelin basic protein-liposome-treated and untreated animals. 246 97

Guinea pigs can be rendered unresponsive to experimental allergic encephalomyelitis (EAE) challenge by prior injections of myelin basic protein (BP) or peptides derived from BP. The synthesized tryptophan-containing peptide (TrpP, corresponding to residues 114-122) which is the primary encephalitogenic sequence in BP (for guinea pigs) had been conjugated to the non-central nervous system protein bovine serum albumin (BSA) and used for EAE challenge. It has been shown in this study that prechallenge treatment with the BSA carrier alone can significantly inhibit the induction of EAE by TrpP-BSA conjugate. That carrier treatment is immunologically specific was determined when prior treatment with cytochrome c did not protect animals from EAE challenge with TrpP conjugated to BSA. In addition, in disease induced with BP or TrpP, and while TrpP did protect guinea pigs challenged with TrpP, it did not protect those challenged with BP. This last finding raises the possibility of a second encephalitogenic sequence in BP or an important role for the carrier in the TrpP conjugate.
...
PMID:Inhibition of experimental allergic encephalomyelitis by carrier administered prior to challenge with encephalitogenic peptide-carrier conjugate. 616 82

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.
...
PMID:Metallothionein treatment reduces proinflammatory cytokines IL-6 and TNF-alpha and apoptotic cell death during experimental autoimmune encephalomyelitis (EAE). 1142 79

A neutral protease present in inguinal and popliteal lymph nodes of rats with acute experimental allergic encephalomyelitis (EAE), rats injected with Freund's adjuvant, and rats that are normal has been found to hydrolyze basic protein present in purified brain and spinal cord myelin. The enzyme has been enriched by ammonium sulfate precipitation, and its properties have been studied. The protease activity toward different substrates was very specific and decreased in the following order: Protamine sulfate = polylysine (MW 183,000) > myelin basic protein > histone > polylysine (MW 2000) > polyarginine > cytochrome c. Other proteins including casein, freshly denatured hemoglobin, egg albumin, bovine serum albumin, and ribonuclease were ineffective as substrates. The pH curve showed a peak at pH7 for rat myelin, isolated beef basic protein, and histone. A possible role for this enzyme in demyelination in acute experimental allergic encephalomyelitis is suggested.
...
PMID:A lymph node neutral proteinase acting on myelin basic protein. 1217 May 91

The nonstructural protein 2C is highly conserved among picornaviruses and plays an important role in the assembly of mature virions, membrane association, and viral RNA synthesis. The investigation of other potential functions of nonstructural protein 2C from avian encephalomyelitis virus (AEV) resulted in identifying for the first time that the protein 2C is involved in apoptosis. Expression of the protein 2C on chick embryo brain (CEB) and Cos-7 cells produced TUNEL-positive cells characterized by a cleavage of cellular DNA and the formation of membrane-enclosed apoptotic bodies. Analysis of the protein 2C showed that the N-terminal domain containing 35 amino acid (aa) residues (between 46 and 80 aa) is associated with apoptotic function. Transfection of the deletion mutant lacking this 35 aa's into CEB and Cos-7 cells failed to induce apoptosis. Furthermore, the protein 2C induced apoptosis in the transfected CEB and Cos-7 cells through activation of caspase-9 rather than caspase-8 followed by activation of caspase-3 pathway. Analysis of the Western blots of caspase-3 and caspase-9 showed the characteristics of active caspase-3 and -9 in the 2C-transfected CEB and Cos-7 cells as seen in the AEV-infected CEB cells while they were in the form of procaspase-3 and procaspase-9 in the 2C mutant-transfected cells. To further elucidate the mechanism of the 2C-induced apoptosis, the 2C-transfected CEB and Cos-7 cells were fractionated into mitochondria and cytosol and subjected for Western blotting, located cytochrome c in the mitochondria as well as the cytosol fractions, while it was only sequestered in the mitochondrial fraction in the mutant 2C-transfected cells. The protein 2C was located in the mitochondria and cytosol of the transfected/infected CEB and transfected Cos-7 cells, but the mutant lost its ability to localize to the mitochondria. Altogether, the results demonstrate that the protein 2C localized to the mitochondria of the transfected cells triggered the efflux of cytochrome c into the cytosol in turn activating the upstream caspase-9 and then the downstream caspase-3, thus leading to apoptosis in the cells.
...
PMID:Avian encephalomyelitis virus nonstructural protein 2C induces apoptosis by activating cytochrome c/caspase-9 pathway. 1497 45

Alphaviruses are mosquito-borne, enveloped, plus-strand RNA viruses that cause a spectrum of diseases in humans that include fever, rash, arthritis, meningitis, and encephalomyelitis. Sindbis virus (SINV) is the prototype alphavirus, causes encephalomyelitis in mice, and provides a model system for studying the pathogenesis of alphavirus-induced neurological disease. Major target cells for SINV infection in the central nervous system (CNS) are neurons, and both host and viral factors determine the fate of infected neurons. Young animals are most susceptible to fatal disease. This correlates with the ability of SINV to induce apoptosis in immature neurons. In vitro, apoptotic death of neuroblastoma cells can be induced by fusion of the virus envelope with the endosomal membrane and does not require infectious virus. This fusion process activates acid sphingomyelinase that cleaves sphingomyelin to release ceramide, an initiator of apoptosis. Within an hour, poly(ADP-ribose) polymerase is activated, and this is followed by release of cytochrome c and activation of effector caspases. SINV-induced cell death can be delayed or prevented by treatment with antioxidants or caspase inhibitors and by intracellular expression of Bcl-2, Beclin-1, or protease inhibitors. Older animals survive infection unless infected with a neurovirulent strain of SINV. In these mice, anterior horn motor neurons die by a primarily necrotic process that is influenced by excitotoxic amino acids and inflammation, whereas hippocampal neurons can be either apoptotic or necrotic. Death also occurs in uninfected neurons in the vicinity of infected neurons and can be delayed or prevented by treatment with glutamate receptor antagonists.
...
PMID:Neuronal cell death in alphavirus encephalomyelitis. 1579 51

Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found in plant products, including red grapes, exhibits anticancer, antioxidant, and anti-inflammatory properties. Using an animal model of multiple sclerosis (MS), we investigated the use of resveratrol for the treatment of autoimmune diseases. We observed that resveratrol treatment decreased the clinical symptoms and inflammatory responses in experimental allergic encephalomyelitis (EAE)-induced mice. Furthermore, we observed significant apoptosis in inflammatory cells in spinal cord of EAE-induced mice treated with resveratrol compared with the control mice. Resveratrol administration also led to significant down-regulation of certain cytokines and chemokines in EAE-induced mice including tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-9, IL-12, IL-17, macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES), and Eotaxin. In vitro studies on the mechanism of action revealed that resveratrol triggered high levels of apoptosis in activated T cells and to a lesser extent in unactivated T cells. Moreover, resveratrol-induced apoptosis was mediated through activation of aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) and correlated with up-regulation of AhR, Fas, and FasL expression. In addition, resveratrol-induced apoptosis in primary T cells correlated with cleavage of caspase-8, caspase-9, caspase-3, poly(ADP-ribose) polymerase, and release of cytochrome c. Data from the present study demonstrate, for the first time, the ability of resveratrol to trigger apoptosis in activated T cells and its potential use in the treatment of inflammatory and autoimmune diseases including, MS.
...
PMID:Resveratrol (trans-3,5,4'-trihydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor. 1787 69

Theiler's murine encephalomyelitis virus (TMEV), a member of the Cardiovirus genus in the family Picornaviridae, is a highly cytolytic virus that produces necrotic death in rodent cells except for macrophages, which undergo apoptosis. In the present study we have analyzed the kinetics of BeAn virus infection in M1-D cells, in order to temporally relate virus replication to the apoptotic signaling events. Apoptosis was associated with early exponential virus growth from 1 to 12 h postinfection (p.i.); however, >/=80% of peak infectivity was lost by 16 to 24 h p.i. The pan-caspase inhibitor qVD-OPh led to significantly higher virus yields, while zVAD-fmk completely inhibited virus replication until 10 h p.i., precluding its assessment in apoptosis. In contrast, while zVAD-fmk significantly inhibited BeAn virus replication in BHK-21 cells at 12 and 16 h p.i., virus replication at these time points was not altered by qVD-OPh. Bax translocation into mitochondria, efflux of cytochrome c into the cytoplasm, and activation of caspases 9 and 3 between approximately 8 and 12 h p.i. (all hallmarks of the intrinsic apoptotic pathway) were transiently inhibited by expression of Bcl-2, which is not expressed in M1-D cells. Thus, BeAn virus infection in M1-D macrophages, which restricts virus replication, provides a potential mechanism for modulating TMEV neurovirulence during persistence in the mouse central nervous system.
...
PMID:Theiler's virus-induced intrinsic apoptosis in M1-D macrophages is Bax mediated and restricts virus infectivity: a mechanism for persistence of a cytolytic virus. 1828 28

Chronic inflammation can associate with autoreactive immune responses, including CD4(+) T cell responses to self-Ags. In this paper, we show that the adipocyte-derived proinflammatory hormone leptin can affect the survival and proliferation of autoreactive CD4(+) T cells in experimental autoimmune encephalomyelitis, an animal model of human multiple sclerosis. We found that myelin olygodendrocyte glycoprotein peptide 35-55 (MOG(35-55))-specific CD4(+) T cells from C57BL/6J wild-type mice could not transfer experimental autoimmune encephalomyelitis into leptin-deficient ob/ob mice. Such a finding was associated with a reduced proliferation of the transferred MOG(35-55)-reactive CD4(+) T cells, which had a reduced degradation of the cyclin-dependent kinase inhibitor p27(kip1) and ERK1/2 phosphorylation. The transferred cells displayed reduced Th1/Th17 responses and reduced delayed-type hypersensitivity. Moreover, MOG(35-55)-reactive CD4(+) T cells in ob/ob mice underwent apoptosis that associated with a downmodulation of Bcl-2. Similar results were observed in transgenic AND-TCR- mice carrying a TCR specific for the pigeon cytochrome c 88-104 peptide. These molecular events reveal a reduced activity of the nutrient/energy-sensing AKT/mammalian target of rapamycin pathway, which can be restored in vivo by exogenous leptin replacement. These results may help to explain a link between chronic inflammation and autoimmune T cell reactivity.
...
PMID:Leptin modulates the survival of autoreactive CD4+ T cells through the nutrient/energy-sensing mammalian target of rapamycin signaling pathway. 2107 10

Mitochondria are essential to neuronal viability and function due to their roles in ATP production, intracellular calcium regulation, and activation of apoptotic pathways. Accordingly, mitochondrial dysfunction has been indicated in a wide variety of neurodegenerative diseases, including Alzheimer's disease (AD), Huntington's disease, amyotrophic lateral sclerosis, stroke, and multiple sclerosis (MS). Recent evidence points to the permeability transition pore (PTP) as a key player in mitochondrial dysfunction in these diseases, in which pathologic opening leads to mitochondrial swelling, rupture, release of cytochrome c, and neuronal death. Reactive oxygen species (ROS), which are inducers of PTP opening, have been prominently implicated in the progression of many of these neurodegenerative diseases. In this context, inactivation of a mitochondria-targeted redox enzyme p66ShcA (p66) has been recently shown to prevent the neuronal cell death leading to axonal severing in the murine model of MS, experimental autoimmune encephalomyelitis (EAE). To further characterize the response of neurons lacking p66, we assessed their reaction to treatment with stressors implicated in neurodegenerative pathways. Specifically, p66-knockout (p66-KO) and wild-type (WT) neurons were treated with hydrogen peroxide (H(2)O(2)) and nitric oxide (NO), and assessed for cell viability and changes in mitochondrial properties, including morphology and ROS production. The results showed that p66-KO neurons had greater survival following treatment with each stressor and generated less ROS when compared to WT neurons. Correspondingly, mitochondria in p66-KO neurons showed diminished morphological changes in response to these challenges. Overall, these findings highlight the importance of developing mitochondria-targeted therapeutics for neurodegenerative disorders, and emphasize p66, mitochondrial ROS, and the PTP as key targets for maintaining mitochondrial and neuronal integrity.
...
PMID:Genetic inactivation of mitochondria-targeted redox enzyme p66ShcA preserves neuronal viability and mitochondrial integrity in response to oxidative challenges. 2283 25

1 2 Next >>