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

Propofol hemisuccinate is a prodrug water soluble form of the lipophilic, phenolic compound propofol (2,6-di-isopropylphenol), that is the active ingredient in the widely used anesthetic agent Diprovan. Propofol binds to GABA(A) receptors but also has a phenolic structure that confers antioxidant properties to the molecule. The effects of propofol hemisuccinate in rat experimental autoimmune encephalomyelitis (EAE) were studied using different doses and time regimes. Propofol hemisuccinate, 100 mg/kg given three times a day from day 7 or day 12 until day 16 after disease initiation, significantly reduced maximal EAE score. Histology studies supported the clinical findings demonstrating reduction in the inflammatory response in the lumbar spinal cord in animals treated with propofol hemisuccinate. Decreased levels of nitrotyrosine and unchanged levels of induced nitric oxide synthase suggest propofol hemisuccinate crossed the blood brain barrier and exerted its effects by lowering reactive oxygen species levels. The results suggest that propofol hemisuccinate may provide an alternative mode of treatment for acute exacerbations of multiple sclerosis.
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PMID:Propofol hemisuccinate suppression of experimental autoimmune encephalomyelitis. 1745 16

Innate immune cells may regulate adaptive immunity by balancing different lineages of T cells and providing negative costimulation. In addition, CD11b(+)Gr-1(+) myeloid-derived suppressor cells have been described in tumor, parasite infection, and severe trauma models. In this study, we observe that splenic CD11b(+) cells markedly increase after experimental autoimmune encephalomyelitis (EAE) immunization, and they suppress T cell proliferation in vitro. Although >80% of CD11b(+) cells express varying levels of Gr-1, only a small population of CD11b(+)Ly-6C(high) inflammatory monocytes (IMC) can efficiently suppress T cell proliferation and induce T cell apoptosis through the production of NO. IFN-gamma produced by activated T cells is essential to induce IMC suppressive function. EAE immunization increases the frequencies of IMC in the bone marrow, spleen, and blood, but not in the lymph nodes. At the peak of EAE, IMC represent approximately 30% of inflammatory cells in the CNS. IMC express F4/80 and CD93 but not CD31, suggesting that they are immature monocytes. Furthermore, IMC have the plasticity to up-regulate NO synthase 2 or arginase 1 expression upon different cytokine treatments. These findings indicate that CD11b(+)Ly-6C(high) IMC induced during EAE priming are powerful suppressors of activated T cells. Further understanding of suppressive monocytes in autoimmune disease models may have important clinical implications for human autoimmune diseases.
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PMID:CD11b+Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis. 1791 8

Ethyl 2-[4-(12-beta-artemisininoxy)]phenoxylpropionate (SM933) is a novel derivative of artemisinin, an herbal compound approved for the treatment of malaria. In this study, we show that SM933 has unique anti-inflammatory properties through regulation of signaling pathways, leading to amelioration of experimental autoimmune encephalomyelitis. The anti-inflammatory properties of SM933 were characterized by inhibition of encephalitogenic T cell responses that were altered to exhibit a Th2 immune deviation and reduced activity and concentration of NO and inducible NO synthase. The observed effect of SM933 was mediated through regulatory mechanisms involving the NFkappaB and the Rig-G/JAB1 signaling pathways. SM933 was found to inhibit the activity of NFkappaB by up-regulating IkappaB, which accounted for various down-stream anti-inflammatory actions. Furthermore, it up-regulated Rig-G through the action of IFN-alpha and prevented JAB1, a master cell cycle regulator, from entering the nucleus to promote p27 degradation, resulting in down-regulation of CDK2 and cyclin A and cell cycle progression. Regulation of the Rig-G/JAB1 pathway by SM933 led to altered cell cycle activity of encephalitogenic T cells as a result of its selective effect on activated, but not resting, T cells. The study indicates that SM933 is a novel anti-inflammatory agent acting through defined signaling mechanisms and provides regulatory mechanisms required for effective drug targeting in treatment of autoimmune disease and inflammation.
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PMID:Anti-inflammatory properties and regulatory mechanism of a novel derivative of artemisinin in experimental autoimmune encephalomyelitis. 1794 69

Reactive oxygen species (ROS) are implicated in the pathogenesis of multiple sclerosis (MS) and its murine model experimental autoimmune encephalomyelitis (EAE). The effect of edaravone, a free radical scavenger, on EAE was investigated in this study. Treatment with edaravone significantly ameliorated the clinical severity of EAE, and a reduced infiltration of lymphocytes was observed based on a histological analysis. The expression of inducible NO synthase (iNOS) in the spinal cords appeared to be reduced by the treatment with edaravone and this effect was confirmed in vitro. A reduction of both the cellular infiltration and the expression of iNOS may therefore underlie the mechanisms of the beneficial effect of edaravone on EAE.
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PMID:Edaravone, a free radical scavenger, ameliorates experimental autoimmune encephalomyelitis. 1857

Lewis rats immunized with guinea pig myelin basic protein residues 68-86 develop acute experimental autoimmune encephalomyelitis and recover. The predominant T cell receptor expressed by the encephalitogenic T cells is TCRBV8S2. They persist in bone marrow many weeks after recovery. CD3 is down-regulated, but >90% express CD4. They fail to proliferate to GPMBP68-86 unless a nitric oxide synthase inhibitor is added to the cultures. Perhaps these are memory T cells that are maintained in a suppressed state in BM by a nitric oxide-dependent mechanism.
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PMID:Myelin basic protein-reactive T cells persist in an inactive state in the bone marrow of Lewis rats that have recovered from autoimmune encephalomyelitis. 1921 Nov 56

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the CNS. Metformin is the most widely used drug for diabetes and mediates its action via activating AMP-activated protein kinase (AMPK). We provide evidence that metformin attenuates the induction of EAE by restricting the infiltration of mononuclear cells into the CNS, down-regulating the expression of proinflammatory cytokines (IFN-gamma, TNF-alpha, IL-6, IL-17, and inducible NO synthase (iNOS)), cell adhesion molecules, matrix metalloproteinase 9, and chemokine (RANTES). Furthermore, the AMPK activity and lipids alterations (total phospholipids and in free fatty acids) were restored by metformin treatment in the CNS of treated EAE animals, suggesting the possible involvement of AMPK. Metformin activated AMPK in macrophages and thereby inhibited biosynthesis of phospholipids as well as neutral lipids and also down-regulated the expression of endotoxin (LPS)-induced proinflammatory cytokines and their mediators (iNOS and cyclooxygenase 2). It also attenuated IFN-gamma and IL-17-induced iNOS and cyclooxygenase 2 expression in RAW267.4 cells, further supporting its anti-inflammatory property. Metformin inhibited T cell-mediated immune responses including Ag-specific recall responses and production of Th1 or Th17 cytokines, while it induced the generation of IL-10 in spleen cells of treated EAE animals. Altogether these findings reveal that metformin may have a possible therapeutic value for the treatment of multiple sclerosis and other inflammatory diseases.
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PMID:Metformin attenuated the autoimmune disease of the central nervous system in animal models of multiple sclerosis. 1949 26

Recent studies have implicated Chlamydia pneumoniae (C. pneumoniae) is present in a subset of patients with multiple sclerosis (MS) in which C. pneumoniae could act as a cofactor in the development of the disease. Macrolide antibiotics are most widely used anti-chlamydial agents and have immunomodulatory effect independently of their anti-bacterial activity. To investigate their effects on experimental autoimmune encephalomyelitis (EAE), EAE was induced by immunization with MBP68-86 peptide emulsified in complete Freund's adjuvant (CFA). Clarithromycin (CM) or azithromycin (AM, 50 mg/100 g body weight) was administrated daily from day 2 before immunization. All rats developed and survived EAE, but the groups administrated CM or AM had more severe symptoms. On day 11 post-immunization, mononuclear cells (MNCs) were prepared from the spleen of control group and cultured with or without macrolide antibiotics (10mug/ml). We evaluated nitric oxide (NO) production in the serum and culture supernatant. Inducible nitric oxide synthase (iNOS) mRNA and protein expression in the spinal cords and cultured MNCs were measured. The results showed that CM and AM similarly inhibited NO production and iNOS mRNA and protein expression in vivo and in vitro. Macrolide antibiotics may aggravate EAE by inhibiting iNOS mRNA and protein expression. Further studies are needed to investigate the effect of macrolide antibiotics on MS and to compare the effect of different anti-chlamydial antibiotics on MS.
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PMID:Macrolide antibiotics aggravate experimental autoimmune encephalomyelitis and inhibit inducible nitric oxide synthase. 1981 24

Although semaphorins were originally identified as axonal guidance molecules during neuronal development, it is emerging that several semaphorins play crucial roles in various phases of immune responses. Sema4D/CD100, a class IV semaphorin, has been shown to be involved in the nervous and immune systems through its receptors plexin-B1 and CD72, respectively. However, the involvement of Sema4D in neuroinflammation still remains unclear. We found that Sema4D promoted inducible NO synthase expression by primary mouse microglia, the effects of which were abolished in plexin-B1-deficient but not in CD72-deficient microglia. In addition, during the development of experimental autoimmune encephalomyelitis (EAE), which was induced by immunization with myelin oligodendrocyte glycoprotein-derived peptides, we observed that the expression of Sema4D and plexin-B1 was induced in infiltrating mononuclear cells and microglia, respectively. Consistent with these expression profiles, when myelin oligodendrocyte glycoprotein-specific T cells derived from wild-type mice were adoptively transferred into plexin-B1-deficient mice or bone marrow chimera mice with plexin-B1-deficient CNS resident cells, the development of EAE was considerably attenuated. Furthermore, blocking Abs against Sema4D significantly inhibited neuroinflammation during EAE development. Collectively, our findings demonstrate the role of Sema4D-plexin-B1 interactions in the activation of microglia and provide their pathologic significance in neuroinflammation.
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PMID:Roles of Sema4D-plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis. 2003 43

Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis. Dark Agouti rats immunized with spinal cord homogenate (SCH) and carbonyl iron (CI), as an adjuvant, develop severe hyperacute form of EAE. They succumb to EAE earlier and have higher clinical scores and lethality rate in comparison to counterparts immunized with SCH + complete Freund's adjuvant. There is no difference in the number of cells or in histological presentation of the CNS infiltrates of rats immunized with the two adjuvants. However, there are more granulocytes, NK and NKT cells, and less CD4(+) T cells in the spinal cord infiltrates of SCH + CI-immunized animals. Nitric oxide (NO)-generating enzyme inducible NO synthase have higher expression in spinal cord of SCH + CI-immunized rats, and this corresponds to more intensive nitrotyrosine formation in the CNS tissue of these rats. Abundant infiltration of granulocytes and NK cells into the CNS and excessive generation of peroxynitrite within the CNS of SCH + CI-immunized rats might account for the severe neurological deficits induced by immunization with CI. These factors should be closely examined in the fulminant forms of multiple sclerosis and acute disseminated encephalomyelitis, as they could represent a promising targets for therapy.
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PMID:It is still not for the old iron: adjuvant effects of carbonyl iron in experimental autoimmune encephalomyelitis induction. 2155 22

Parasitic infections frequently lead to immune deviation or suppression. However, the application of specific parasitic molecules in regulating autoimmune responses remains to be explored. Here we report on the immune modulatory function of Lacto-N-fucopentaose III (LNFPIII), a schistosome glycan, in an animal model for multiple sclerosis. We found that LNFPIII treatment significantly reduced the severity of experimental autoimmune encephalomyelitis (EAE) and CNS inflammation, and skewed peripheral immune response to a Th2 dominant profile. Inflammatory monocytes (IMCs) purified from LNFPIII-treated mice had increased expression of nitric oxide synthase 2, and mediated T cell suppression. LNFPIII treatment also significantly increased mRNA expression of arginase-1, aldehyde dehydrogenase 1 subfamily A2, indoleamine 2,3-dioxygenase and heme oxygenase 1 in splenic IMCs. Furthermore, LNFPIII treatment significantly reduced trafficking of dendritic cells across brain endothelium in vitro. In summary, our study demonstrates that LNFPIII glycan treatment suppresses EAE by modulating both innate and T cell immune response.
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PMID:Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis. 2226 36


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