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)

Estrogen treatment has been found to have suppressive activity in several models of autoimmunity. To investigate the mechanism of 17 beta-estradiol (E2) suppression of experimental autoimmune encephalomyelitis, we evaluated E2 effects on TNF-alpha expression in the central nervous system (CNS) and spleen of C57BL/6 mice immunized with MOG 35-55/CFA. Kinetic analysis demonstrated that E2 treatment drastically decreased the recruitment of total inflammatory cells as well as TNF-alpha(+) macrophages and T cells into the CNS at disease onset. In contrast, E2 had only moderate effects on the relatively high constitutive TNF-alpha expression by resident CNS microglial cells. E2 treatment also had profound inhibitory effects on expression of TNF-alpha by splenic CD4(+) T cells, including those responsive to MOG 35-55 peptide. We propose that the mechanism of E2 protection may involve both systemic inhibition of TNF-alpha expression and local (CNS) recruitment of inflammatory cells, with modest effects on TNF-alpha expression by resident CNS microglial cells.
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PMID:Estrogen inhibits systemic T cell expression of TNF-alpha and recruitment of TNF-alpha(+) T cells and macrophages into the CNS of mice developing experimental encephalomyelitis. 1189 Jul 14

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune demyelinating disease commonly used to model the pathogenetic mechanisms involved in multiple sclerosis (MS). In this study, we examined the effects of immunization with the myelin oligodendrocyte glycoprotein MOG(35-55) on the expression of molecules of the innate immune system, namely toll-like receptor 2 (TLR2) and CD14. Expression of the mRNA encoding TLR2 increased in the choroid plexus, the leptomeninges and within few isolated cells in the CNS parenchyma 4 to 8 days after immunization with MOG. At day 10, the signal spread across the meninges, few perivascular regions and over isolated groups of parenchymal cells. Three weeks after the MOG treatment, at which time animals showed severe clinical symptoms, a robust expression of both TLR2 and CD14 transcripts occurred in barrier-associated structures, as well as parenchymal elements of the spinal cord, and within numerous regions of the brain including, the medulla, cerebellum and the cortex. Dual labeling provided the anatomical evidence that microglia/macrophages were positive for TLR2 in the brain of EAE mice. The regions that exhibited chronic expression of TLR2 and CD14 were also associated with an increase in NF-kappaB activity and transcriptional activation of genes encoding numerous proinflammatory molecules. The present data provide evidence that receptors of the pathogen-associated molecular patterns are strongly induced in the CNS of EAE mice, further reinforcing the concept that the innate immune system plays a determinant role in this autoimmune demyelinating disease.
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PMID:The clinical course of experimental autoimmune encephalomyelitis is associated with a profound and sustained transcriptional activation of the genes encoding toll-like receptor 2 and CD14 in the mouse CNS. 1214 99

B7 costimulatory molecules play an important role in inducing autoimmunity, tumor immunity, and transplant rejection, and therapeutic manipulation of B7 is being investigated in human diseases. To determine whether B7 costimulation is essential for inducing autoimmunity on different genetic backgrounds, we backcrossed B7.1/B7.2 deficient ((-/-)) mice on to the C57BL/6 (B6) and SJL backgrounds and induced experimental autoimmune encephalomyelitis (EAE) in these mice. B7.1/B7.2(-/-) mice on the B6 background were resistant to EAE induced with MOG 35-55, whereas the SJL B7.1/B7.2(-/-) mice were susceptible to PLP 139-151 or PLP 178-191-induced EAE. The SJL B7.1/B7.2(-/-) mice had a qualitatively different lesion pattern in that they showed increased white matter vacuolation compared to wild-type SJL mice when immunized with either PLP 139-151 or PLP 178-191. (B6xSJL)F1 B7.1/B7.2(+/+) mice were susceptible to EAE whereas (B6xSJL)F1 B7.1/B7.2(-/-) mice were resistant to EAE induced with either encephalitogenic peptide. Thus, genetic background determines the B7 requirement for inducing autoimmunity. These data have important implications for developing B7-based immunotherapies for human diseases.
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PMID:Genetic background determines the requirement for B7 costimulation in induction of autoimmunity. 1220 54

It is well established that CD4(+) T cells are of central importance in mediating the autoimmune destruction associated with the neurological demyelinating disease Multiple sclerosis (MS) and the rodent model of MS, EAE (experimental allergic encephalomyelitis). However, other cells also play a critical role in the inflammatory events that lead to the varying degrees of myelin and axonal damage observed in this disease syndrome. In this review, we present evidence that mast cells, best studied in the context of allergic disease, contribute to EAE disease pathology. Using mast cell-deficient mice, we demonstrate that mast cells are necessary for the full manifestation of MOG-induced EAE disease and show that cross-linking of Fc receptors is one mechanism of mast cell activation in disease. In addition, we provide evidence that mast cells exert influences outside the CNS, perhaps through the effects on the generation of the anti-MOG T cell response.
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PMID:Mechanisms underlying mast cell influence on EAE disease course. 1221 11

Voltage-gated sodium channels contribute to the development of axonal degeneration in white matter, and sodium channel blocking drugs are known to have a protective effect on acutely injured white matter axons. To determine whether phenytoin has a protective effect on axons in a neuroinflammatory model, we studied the effect of phenytoin on axonal degeneration in the optic nerve in MOG-induced experimental allergic encephalomyelitis (EAE). We report that, whereas approximately 50% of optic nerve axons are lost at 27-28 days in untreated EAE, only approximately 12% of the axons are lost if mice with MOG-induced EAE are treated with phenytoin. These results demonstrate that it is possible to achieve substantial protection of white matter axons in EAE, a model neuroinflammatory/demyelination disease, with a sodium channel blocking agent.
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PMID:Neuroprotection of axons with phenytoin in experimental allergic encephalomyelitis. 1239 89

Previous studies have shown that immunization of the Lewis rat with myelin basic protein (MBP), an encephalitogenic antigen derived from the myelin sheath of the CNS, induced both experimental autoimmune encephalomyelitis (EAE) and anterior uveitis (AU). In the current study, we show that a major peptide derived from another encephalitogenic myelin protein-the myelin/oligodendrocyte glycoprotein (MOG35-55)-induced both encephalomyelitis and uveitis in (B6 x SJL) F1 and wt-B6 mice. Pathological studies documented that an anterior uveitis was induced by MOG35-55. A similar disease pattern was induced by either active immunization with peptideMOG35-55 (pMOG35-55) or adoptive transfer of MOG35-55-specific T cells. The induced uveitis persisted for >60 days without remission. Our studies demonstrate for the first time that MOG is uveitogenic in mice that express the H-2(b) genetic background. This new experimental model should provide a useful tool for the study of the pathogenesis of chronic AU and determination of the pathogenic mechanisms by which a large portion of MS patients develops uveitis.
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PMID:Induction of autoimmune encephalomyelitis and uveitis in B6 and (B6 x SJL) mice by peptides derived from myelin/oligodendrocyte glycoprotein. 1241 41

The chemokine monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 have been shown to play an important role in the migration and trafficking of macrophages and Th1 effector cells in experimental autoimmune encephalomyelitis. Also, MCP-1 has been reported to regulate oral tolerance induction by inhibition of Th1 cell-related cytokines and by the ability of Abs to MCP-1 to inhibit oral tolerance. This study demonstrates that neither MCP-1 nor its receptor CCR2 is required for the induction of oral tolerance. Mice deletional for either MCP-1 or CCR2 had suppressed cell-proliferative and Th1 responses following oral administration and immunization with myelin oligodendrocyte glycoprotein (MOG(35-55)). TGF-beta was up-regulated in fed and immunized deletional mice, while IL-4 was absent from deletional mice, but up-regulated in controls. Decreased experimental autoimmune encephalomyelitis severity was found in MOG(35-55)-fed MCP-1 deletional mice, indicating induction of oral tolerance. These results demonstrate that MCP-1 is not required for induction of oral tolerance and that MCP-1 and CCR2 are essential for up-regulation of IL-4 in tolerized mice.
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PMID:Induction of low dose oral tolerance in monocyte chemoattractant protein-1- and CCR2-deficient mice. 1259 53

The severity of the experimental autoimmune encephalomyelitis (EAE) induced by peptide myelin oligodendrocyte glycoprotein(35-55)(pMOG(35-55)) is thought to be predominantly influenced by the major histocompatibility complex (MHC), so that C57BL6/J mice, on H2(b) strain, were only mildly sick. However, it remains unclear as to how non-MHC gene regions affect EAE. To determine whether the immunization protocol could have an influence on clinical signs, C57BL6/J mice were immunized with a multiple antigen peptide (MAP) containing eight pMOG(35-55)branches synthesized directly onto a lysine core, myelin oligodendrocyte glycoprotein (35-55)-multiple antigen peptide (MOG(35-55)-MAP), in complete Freund's adjuvant (CFA). In most of the mice, clinical onset (marked weakness) occurred approximately at day 15. All mice injected with MOG(35-55)-MAP had more severe symptoms than those injected with pMOG(35-55), which developed no leg paralysis. All MOG(35-55)-MAP-immunized mice developed EAE symptoms, but 50% had primary-progressive EAE, while the other 50% had relapsing-remitting disease. Leukocyte infiltrations, associated with increased glial fibrillary acidic protein (GFAP) expression by reactive astrocytes, were observed around the lateral ventricles and blood vessels in the brain. Significant positive correlations were established between anti-MOG(35-55)antibody levels and clinical scores or GFAP positivity in the spinal cord. The heterogeneity of EAE progression, observed in these genetically identical individuals, suggests that the environment rather than the genetics plays a role. This observation is highly pertinent as it corresponds to what is seen in clinical MS.
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PMID:Optimization of an animal model of experimental autoimmune encephalomyelitis achieved with a multiple MOG(35-55)peptide in C57BL6/J strain of mice. 1260 12

To find immune mechanisms underlying relapse regulation, we developed a model of relapsing-remitting experimental autoimmune encephalomyelitis (EAE) in (B6xSJL) F1 (H-2(b/s)) mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG(35-55)) and compared with low/non-relapsing B6 (H-2(b)) mice. In relapsing H-2(b/s) mice, inflammatory lesions scattered throughout the white matter with extensive demyelination, consisted of CD4(+) T and B220(+) B cells with fewer Mac3(+) macrophages. Memory T cell proliferation to MOG(35-55) was significantly enhanced. Switch of macrophage chemoattractant protein-1 (MCP-1) production from GFAP(+) astrocytes to CD3(+) T cells was observed. Distinct patterns of inflammation and demyelination, MOG(35-55) memory T cell response and regulation of MCP-1 are associated with relapsing H-2(b/s) phenotype.
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PMID:Distinct immune regulation of the response to H-2b restricted epitope of MOG causes relapsing-remitting EAE in H-2b/s mice. 1262 Jun 41

Infections often precede the development of autoimmunity. Correlation between infection with a specific pathogen and a particular autoimmune disease ranges from moderately strong to quite weak. This lack of correspondence suggests that autoimmunity may result from microbial activation of a generic, as opposed to pathogen-specific host-defense response. The Toll-like receptors, essential to host recognition of microbial invasion, signal through a common, highly conserved pathway, activate innate immunity, and control adaptive immune responses. To determine the influence of Toll/IL-1 signaling on the development of autoimmunity, the responses of wild-type (WT) mice and IL-1R-associated kinase 1 (IRAK1)-deficient mice to induction of experimental autoimmune encephalomyelitis were compared. C57BL/6 and B6.IRAK1-deficient mice were immunized with MOG 35-55/CFA or MOG 35-55/CpG DNA/IFA. WT animals developed severe disease, whereas IRAK1-deficient mice were resistant to experimental autoimmune encephalomyelitis, exhibiting little or no CNS inflammation. IRAK1-deficient T cells also displayed impaired Th1 development, particularly during disease induction, despite normal TCR signaling. These results suggest that IRAK1 and the Toll/IL-1 pathway play an essential role in T cell priming, and demonstrate one means through which innate immunity can control subsequent development of autoimmunity. These findings may also help explain the association between antecedent infection and the development or exacerbations of some autoimmune diseases.
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PMID:IL-1 receptor-associated kinase 1 regulates susceptibility to organ-specific autoimmunity. 1262 33


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