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)

DNA vaccination represents a novel means of expressing Ag in vivo for the generation of both humoral and cellular immune responses. The current study uses this technology to elicit protective immunity against experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease of the central nervous system that serves as an experimental model for multiple sclerosis. RT-PCR verified by Southern blotting and sequencing of PCR products of four different C-C chemokines, macrophage-inflammatory protein-1alpha (MIP-1alpha), monocyte-chemotactic protein-1 (MCP-1), MIP-1beta, and RANTES, were performed on brain samples from EAE rats to evaluate mRNA transcription at different stages of disease. Each PCR product was then used as a construct for naked DNA vaccination. The subsequent in vivo immune response to MIP-1alpha or MCP-1 DNA vaccines prevented EAE, even if disease was induced 2 mo after administration of naked DNA vaccines. In contrast, administration of the MIP-1beta naked DNA significantly aggravated the disease. Generation of in vivo immune response to RANTES naked DNA had no notable effect on EAE. MIP-1alpha, MCP-1, and MIP-1beta mRNA transcription in EAE brains peaked at the onset of disease and declined during its remission, whereas RANTES transcription increased in EAE brains only following recovery. Immunization of CFA without the encephalitogenic epitope did not elicit the anti-C-C chemokine regulatory response in DNA-vaccinated rats. Thus, modulation of EAE with C-C chemokine DNA vaccines is dependent on targeting chemokines that are highly transcribed at the site of inflammation at the onset of disease.
 ...
PMID:Long-lasting protective immunity to experimental autoimmune encephalomyelitis following vaccination with naked DNA encoding C-C chemokines. 978 Jan 52

Theiler's murine encephalomyelitis virus is an endemic murine pathogen that induces a demyelinating disease of the central nervous system in susceptible mouse strains. The disease is characterized by central nervous system mononuclear cell infiltration and presents as chronic, progressive paralysis. The expression of CC and C-x-C chemokines in the central nervous system of Theiler's murine encephalomyelitis virus-infected mice was examined throughout the disease course by ELISA and RT - PCR analysis. Central nervous system expression of MCP-1 and MIP-1alpha protein was evident by day 11 post Theiler's murine encephalomyelitis virus infection of SJL mice and continued throughout disease progression. MIP-1alpha, RANTES, MCP-1, C10, IP-10, and MIP-1beta mRNA was specifically expressed in the central nervous system and not the periphery following Theiler's murine encephalomyelitis virus infection. This was associated with development of clinical disease. These data suggest that the expression of multiple chemokines at particular times following viral infection is associated with demyelinating disease.
 ...
PMID:Central nervous system chemokine expression during Theiler's virus-induced demyelinating disease. 1060 4

DA, GDVII and H101 are neurovirulent strains of Theiler's murine encephalomyelitis virus that cause very different neuropathology and CNS disease when inoculated into SJL/J mice. DA virus causes a chronic demyelinating disease, GDVII virus causes an acute fatal polioencephalomyelitis, and H101 virus causes an acute pachymeningitis with hydrocephalus. Performing RNase protection assays, we detected the same pattern of chemokine (RANTES, MCP-1, IP-10, MIP-1beta, MIP-1alpha and MIP-2) mRNA expression in brain and spinal cord during all three infections. In contrast, IFN-beta and IL-6 mRNA were highly expressed only in GDVII virus infection, whereas high levels of LT-alpha mRNA were only found during DA virus infection. Our study demonstrates that proinflammatory cytokines are involved in the neuropathogenesis of CNS disease and modulate the acute and chronic process underlying different pathologic features of disease.
 ...
PMID:Alterations in cytokine but not chemokine mRNA expression during three distinct Theiler's virus infections. 1068 11

The perivascular transmigration and accumulation of macrophages and T lymphocytes in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) may be partly regulated by low m.w. chemotactic cytokines. Using the RNase protection assay and ELISA, we quantified expression of chemokines and chemokine receptors in the spinal cord (SC), brain, and lymph nodes of BV8S2 transgenic mice that developed or were protected from EAE by vaccination with BV8S2 protein. In paralyzed control mice, the SC had increased cellular infiltration and strong expression of the chemokines RANTES, IFN-inducible 10-kDa protein, and monocyte chemoattractant protein-1 and the cognate chemokine receptors CCR1, CCR2, and CCR5, with lower expression of macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2; whereas brain had less infiltration and a lower expression of a different pattern of chemokines and receptors. In TCR-protected mice, there was a decrease in the number of inflammatory cells in both SC and brain. In SC, the reduced cellular infiltrate afforded by TCR vaccination was commensurate with profoundly reduced expression of chemokines and their cognate chemokine receptors. In brain, however, TCR vaccination did not produce significant changes in chemokine expression but resulted in an increased expression of CCR3 and CCR4 usually associated with Th2 cells. In contrast to CNS, lymph nodes of protected mice had a significant increase in expression of MIP-2 and MIP-1beta but no change in expression of chemokine receptors. These results demonstrate that TCR vaccination results in selective reduction of inflammatory chemokines and chemokine receptors in SC, the target organ most affected during EAE.
 ...
PMID:Reduced chemokine and chemokine receptor expression in spinal cords of TCR BV8S2 transgenic mice protected against experimental autoimmune encephalomyelitis with BV8S2 protein. 1072 56

Macrophage inflammatory protein (MIP)-1alpha is a chemokine that is associated with Th1 cytokine responses. Expression and antibody blocking studies have implicated MIP-1alpha in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). We examined the role of MIP-1alpha and its CCR5 receptor in the induction of EAE by immunizing C57BL / 6 mice deficient in either MIP-1alpha or CCR5 with myelin oligodendrocyte glycoprotein (MOG). We found that MIP-1alpha-deficient mice were fully susceptible to MOG-induced EAE. These knockout animals were indistinguishable from wild-type mice in Th1 cytokine gene expression, the kinetics and severity of disease, and infiltration of the central nervous system by lymphocytes, macrophages and granulocytes. RNase protection assays showed comparable accumulation of mRNA for the chemokines interferon-inducible protein-10, RANTES, macrophage chemoattractant protein-1, MIP-1beta, MIP-2, lymphotactin and T cell activation gene-3 during the course of the disease. CCR5-deficient mice were also susceptible to disease induction by MOG. The dispensability of MIP-1alpha and CCR5 for MOG-induced EAE in C57BL / 6 mice supports the idea that differential chemokine expression patterns represent differences in disease mechanism that underlie various models of EAE, and possibly distinct patterns of pathology seen in MS.
 ...
PMID:Induction of experimental autoimmune encephalomyelitis in C57BL/6 mice deficient in either the chemokine macrophage inflammatory protein-1alpha or its CCR5 receptor. 1082 Mar 88

Experimental autoimmune encephalomyelitis (EAE) is a T helper 1 (Th1) cell mediated demyelinating disease and the principal animal model for multiple sclerosis. Spinal cords from SJL mice primed with proteolipid protein peptide 139-151 (pPLP) expressed the chemokines RANTES, MCP-1, MIP-2, KC, MIP-1alpha, MIP-1beta, Mig, and fractalkine. We also identified IP-10 in these samples and described a sequence polymorphism in this transcript. Chemokine expression was specific for tissues of the central nervous system. MCP-1, IP-10, and MIP-2 RNA expression significantly correlated with clinical score. Chemokine receptor expression generally correlated with ligand expression. pPLP-primed mice expressed the Th1-associated markers CCR5 and CXCR3 on mononuclear cells. In addition, cells expressing CCR1, CCR2, CCR3, CCR4, CCR8, and CXCR2 were detected. Here we demonstrate that altered peptide ligand (APL)-induced protection from EAE was accompanied by modulation of chemokine and chemokine receptor expression. Spinal cord tissue sections from APL-protected mice showed greatly reduced levels of all chemokines and of CCR1, CCR5, CCR8, CXCR2 and CXCR3. The Th2-associated chemokine receptors CCR3 and CCR4 were found in protected mice, supporting the hypothesis that Th1 but not Th2 cells are down-regulated by APL treatment. This report concludes that chemokines and chemokine receptors can be useful tools to follow modulation of autoimmune disease.
 ...
PMID:Modulation of experimental autoimmune encephalomyelitis: effect of altered peptide ligand on chemokine and chemokine receptor expression. 1102 50

Astrocytes are specialized cells of the CNS that are implicated in the pathogenesis of multiple sclerosis and experimental allergic encephalomyelitis. In acute and relapsing-remitting experimental allergic encephalomyelitis, the neutrophil chemoattractant CXC chemokines macrophage-inflammatory protein (MIP)-2 and KC are associated with reactive astrocytes in the parenchyma. In vitro treatment of primary astrocyte cultures with nanomolar concentrations of MIP-2 or KC markedly up-regulated expression of the monocyte/T cell chemoattractants monocyte chemoattractant protein-1, inflammatory protein-10, and RANTES by a mechanism that includes stabilization of mRNA. Production of TNF-alpha and IL-6 transcripts were also noted, as was autocrine induction of MIP-2 and KC message. In addition, low levels of MIP-1alpha and MIP-1beta were induced following treatment with MIP-2 or KC. These effects are specific to astrocytes as MIP-2 treatment of microglial cells failed to elicit chemokine production. The astrocyte chemokine receptor for MIP-2 has 2.5 nM affinity for ligand. Astrocytes from CXCR2-deficient mice still respond to KC and MIP-2, indicating the presence of an alternative or novel high affinity receptor for these ligands. We propose that this KC/MIP-2 chemokine cascade may contribute to the persistence of mononuclear cell infiltration in demyelinating autoimmune diseases.
 ...
PMID:Macrophage inflammatory protein-2 and KC induce chemokine production by mouse astrocytes. 1103 12

Recent evidence suggests that T-lymphocyte extravasation and CNS-parenchymal infiltration during autoimmune disease might be regulated by antigen-presenting (ED2(+)) cerebral/spinal perivascular phagocytes (CPP/SPP). Since the massive erythrocytic and leukocytic infiltrates in the CNS of rats with experimental allergic encephalomyelitis do not allow a precise differentiation between CPP/SPP and the invading cells in the Virchow-Robin space, we developed a new immune-response model whereby the extravasation of T-lymphocytes was not followed by other blood cells. Adult Lewis rats were sensitized to horseradish peroxidase (HRP). Subsequent intracerebroventricular (i.c.v.) injections of HRP and/or Fluoro-Emerald (FE) served to: (1) challenge the primed T-lymphocytes and (2) label the CPP/SPP for additional immunocytochemical analysis. We found that 24 h and 3 days after single, double, or triple antigen boosting T-lymphocytes (R73(+), W3/25(+), OX50(+)) entered the Virchow-Robin space but did not break through the astrocytic glia limitans. Instead they adhered to HRP-containing activated CPP/SPP (mabs OX-6(+), SILK6(+), CD40(+), CD80(+), CD86(+)). This selective contact was mediated neither by cell adhesion molecules (P-selectin, ICAM-1, VCAM-1), nor promoted by chemokine receptors (CCR1, CCR5) or chemokines (monocyte chemoattractant protein (MCP)-1, MIP-1alpha, MIP-1beta, RANTES). This non-inflammatory, but antigen-dependent lymphocyte extravasation provides optimal conditions to further study the CNS immune response.
 ...
PMID:Exogenous antigen containing perivascular phagocytes induce a non-encephalitogenic extravasation of primed lymphocytes. 1143 Oct 2

In this study, we examined the role of CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta, and CCL5/RANTES during recurrent anterior uveitis (RAU). LEW rats injected with myelin basic protein (MBP) developed experimental autoimmune encephalomyelitis (EAE) and associated anterior uveitis (AU), which was mediated by CD4(+) T cells. After recovery, rats become resistant to EAE but developed RAU. Rats reinjected with MBP developed RAU without EAE. The chemokines tested were detected in the eye at RAU accelerated onset, increased as the disease progressed, and fell as clinical signs improved. At the same time, in the spinal cords of rats, these chemokines were still detected but at reduced levels. Administration of anti-MIP-1alpha neutralizing antibodies resulted in almost complete suppression of clinical RAU and significant reduction of inflammatory cell recruitment into the iris. Anti-MIP-1beta and anti-MCP-1 antibodies were effective in suppression of RAU but to lesser degree. Treatment with anti-RANTES antibodies was not effective in protecting against the recurrent development of the disease. In the eyes, the message for CCR1 and CCR5 was considerably elevated prior to the onset of AU and decreased after treatment with anti-chemokine antibodies. Our results suggest a crucial role of CCL3/MIP-1alpha in the development of RAU in Lewis rats. In addition, CCL2/MCP-1 and CCL4/MIP-1beta may also play a role in immunopathogenesis of RAU.
 ...
PMID:Crucial role of CCL3/MIP-1alpha in the recurrence of autoimmune anterior uveitis induced with myelin basic protein in Lewis rats. 1214 7

Chronic relapsing experimental autoimmune encephalomyelitis (ChREAE) is an autoimmune disease of the central nervous system (CNS) induced by CNS myelin components. In the early active stage, both ChREAE and multiple sclerosis (MS) are characterized by the presence of perivascular inflammatory cuffs disseminated in the CNS. There is growing evidence that chemoattractant cytokines (chemokines) play an important role in this process. The main goal of the present study was to analyse the hypothesis that chemokine expression in the CNS during autoimmune inflammation is regulated by proinflammatory cytokines. To address this concept, we analysed temporal relations between chemokine and cytokine expression during ChREAE. Phasic upregulation of gene expression for chemokines T-cell activation gene 3 (TCA-3)/CCL1, monocyte chemoattractant protein-1 (MCP-1)/CCL2, macrophage inflammatory protein-1 alpha (MIP-1alpha)/CCL3, MIP-1beta/CCL4, regulated on activation normal T cell expressed and secreted (RANTES)/CCL5 and MIP-2/CXCL2-3 as well as cytokines tumour necrosis factor-alpha (TNF-alpha), -beta, LT-beta, interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) in the CNS was observed during attacks of ChREAE. Expression of cytokines TNF-beta and LT-beta preceded, and the expression of TGF-beta1 followed chemokine upregulation. Our results suggest that chemokine expression during CNS autoimmune inflammation may be regulated by some proinflammatory cytokines.
 ...
PMID:Chemokine upregulation follows cytokine expression in chronic relapsing experimental autoimmune encephalomyelitis. 1282 62


1 2 Next >>