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)

Chemokines are a family of low molecular mass proteins with chemotactic and cell activating activities. Reverse transcription-polymerase chain reaction and Northern hybridization were used to examine their expression during murine experimental allergic encephalomyelitis (EAE), an autoimmune disease used as a model of multiple sclerosis. The mRNAs encoding RANTES, MIP-1 alpha, MIP-1 beta, TCA3 (I-309), IP-10, JE (MCP-1), KC (MGSA/gro), and MARC (MCP-3) were induced in the spinal cord 1-2 days before clinical signs were apparent. SDF, a cDNA predicted to encode a chemokine-like product, was expressed in normal as well as diseased spinal cords. No expression of C10 or MIP-2 was detected. Activated encephalitogenic T cells expressed message for RANTES, MIP-1 alpha, MIP-1 beta, and TCA3. These results define a subset of chemokines that may play an important role in the inflammatory process during murine EAE.
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PMID:Chemokine expression in murine experimental allergic encephalomyelitis. 753 12

Mononuclear leukocytes preferentially accumulate in the central nervous system (CNS) during the course of experimental autoimmune encephalomyelitis (EAE). To address factors that govern leukocyte trafficking in EAE, we monitored expression of mRNAs encoding IP-10 and JE/MCP-1, which are members of a family of chemoattractant cytokines. A transient burst of IP-10 and JE/MCP-1 mRNA accumulation in the CNS occurred, in close relation to the onset of histologic and clinical disease. In situ hybridizations showed, unexpectedly, that astrocytes were the major source of mRNAs encoding IP-10 and JE/MCP-1. These observations implicate astrocyte-derived cytokines as potential chemoattractants for inflammatory cells during EAE.
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PMID:Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis. 847 96

Peripheral antigen-specific tolerance can be induced by feeding protein antigens. The mechanism has been described as either clonal anergy/deletion or induction of antigen-specific regulatory cells that produce transforming growth factor (TGF)-beta, depending on the dose of antigen fed. Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, can be prevented by feeding myelin basic protein (MBP) or proteolipid protein (PLP). We decided to address the role of chemokines in the induction of oral tolerance. We have used a model antigen system of feeding a high dose of human gamma globulin (HGG) to mice that have been subsequently immunized with HGG emulsified in CFA. The result was decreased recall proliferative, delayed-type hypersensitivity (DTH) and Th1 cytokine responses. By contrast, Th2 cytokine responses were enhanced. Interestingly, macrophage inflammatory protein (MIP)-1alpha production was decreased, whereas monocyte chemotactic protein (MCP)-1 production was enhanced. Induction of oral tolerance was prevented by the administration of anti-MCP-1 to mice fed HGG. These results show that chemokines play an important role in the induction of oral tolerance.
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PMID:The role of chemokines in oral tolerance. Abrogation of nonresponsiveness by treatment with antimonocyte chemotactic protein-1. 861 Sep 67

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune demyelinating disease of the central nervous system that serves as an animal model for multiple sclerosis. Antigen-specific tolerance regimens, including oral tolerance, have been used prophylactically to prevent development of acute EAE as well as a number of other autoimmune diseases. Two mechanisms have been proposed to explain the immunologic basis for disease inhibition: bystander immune suppression and clonal anergy/deletion. This report demonstrates a novel mechanism for monocyte chemotactic protein (MCP)-1 as a regulatory factor of oral tolerance. Oral administration of proteolipid protein peptide (PLP139-151) increased MCP-1 expression in the intestinal mucosa, Peyer's patch, and mesenteric lymph nodes. Increase in MCP-1 expression resulted in downregulation of mucosal interleukin (IL)-12 expression with concomitant increase in mucosal IL-4 expression. Functionally, MCP-1 upregulation was shown to regulate oral tolerance induction by the ability of antibodies to MCP-1 to inhibit tolerance induction. The anti-MCP-1 abrogation of oral tolerance induction also resulted in restoration of mucosal IL-12 expression as well as peripheral antigen-specific T helper cell 1 responses. These results demonstrate a novel and important role for MCP-1 in the regulation or oral tolerance for the prevention and treatment of autoimmune disease.
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PMID:Monocyte chemotactic protein 1 regulates oral tolerance induction by inhibition of T helper cell 1-related cytokines. 948 Sep 83

Infection of C57BL/6 mice with the V5A13.1 strain of mouse hepatitis virus (MHV-V5A13.1) results in an acute encephalomyelitis and chronic demyelinating disease with features similar to the human demyelinating disease multiple sclerosis. Chemokines are a family of proinflammatory cytokines associated with inflammatory pathology in various diseases. The kinetics and histologic localization of chemokine production in the central nervous system of MHV-infected mice were examined to identify chemokines that contribute to inflammation and demyelination. Transcripts for the chemokines cytokine-response gene-2 (CRG-2), regulated on activation, normal T cell expressed and secreted (RANTES), macrophage-chemoattractant protein-1 and protein-3 (MCP-1, MCP-3), macrophage-inflammatory protein-1beta (MIP-1beta), and MIP-2 were detected in the brains of MHV-infected mice at 3 days postinfection (p.i.), and these transcripts were increased markedly in brains and spinal cords at day 7 p.i., which coincides with the occurrence of acute viral encephalomyelitis. By day 35 p.i., RANTES, CRG-2, and MIP-1beta were detected in brains and spinal cords of mice with chronic demyelination. CRG-2 mRNA expression colocalized with viral RNA and was associated with demyelinating lesions. Astrocytes were the predominant cell type expressing CRG-2 mRNA. These observations suggest a role for chemokines, notably CRG-2, in the initiation and maintenance of an inflammatory response following infection with MHV, which is important in contributing to demyelination.
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PMID:Dynamic regulation of alpha- and beta-chemokine expression in the central nervous system during mouse hepatitis virus-induced demyelinating disease. 955 36

Experimental autoimmune encephalomyelitis (EAE) is a T lymphocyte-mediated disease of the central nervous system (CNS), characterized by mononuclear cell infiltration and demyelination resulting in paralysis. We examined CC chemokine expression in the CNS throughout the entire course of the disease and found that the production of macrophage inflammatory protein (MIP)-1alpha correlated with increasing acute disease severity and remained elevated throughout chronic, relapsing disease. In contrast, a substantial level of monocyte chemotactic protein (MCP)-1 expression was not observed until late in acute disease and continued to be evident in the relapsing phase of the disease. MCP-1 expression correlated with increasing severity of clinical relapses. Lower levels of RANTES in the CNS were noted throughout the disease course, but showed little correlation with either acute or relapsing disease. Although RANTES expression was observed during the entire course of disease, anti-RANTES treatment had no effect on clinical disease progression. Anti-MCP-1, but not anti-MIP-1alpha, treatment during relapsing EAE decreased clinical severity of relapsing disease. Furthermore, anti-MCP-1 treatment reduced CNS macrophage accumulation during relapsing EAE. These results suggest that MIP-1alpha controls mononuclear cell accumulation during acute EAE, while MCP-1 controls mononuclear cell infiltration during relapsing EAE.
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PMID:Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1alpha and monocyte chemotactic protein-1. 991 84

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) considered to be an animal model for multiple sclerosis (MS). The detailed mechanism that specifies accumulation of inflammatory cells within the CNS in these conditions remains a subject of active investigation. Chemokines including IP-10, GRO-alpha, MCP-1 are produced in EAE tissues selectively by parenchymal astrocytes, but the regulatory stimuli that govern this expression remain undetermined. The unexpected occurrence of increased EAE susceptibility in Balb/c GKO mice (lacking IFN-gamma) offered an opportunity to examine the spectrum of chemokine expression during immune-mediated inflammation in the absence of a single regulatory cytokine. We found that chemokines MCP-1 and GRO-alpha were upregulated in the CNS of mice with EAE despite the GKO genotype. IP-10, which is highly expressed in the CNS of mice with an intact IFN-gamma gene and EAE, was strikingly absent. In vitro experiments confirmed that IFNgamma selectively stimulates astrocytes for IP-10 expression. These results indicate that IP-10 is dependent upon IFN-gamma for its upregulation during this model disease, and document directly that astrocyte expression of chemokines during EAE is governed by pro-inflammatory cytokines.
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PMID:Chemokine expression in GKO mice (lacking interferon-gamma) with experimental autoimmune encephalomyelitis. 1019 Jun 95

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the central nervous system (CNS). RT-PCR verified by Southern blotting and sequencing of PCR products of two C-C chemokines, MIP-1alpha and MCP-1, was performed on brain samples from EAE rats to evaluate mRNA transcription of these chemokines at different stages of disease. mRNA transcription in of each chemokine peaked after the onset of disease and declined during its remission. 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. Immunization of CFA without the encephalitogenic epitope did not elicit an 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.
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PMID:Prevention of experimental autoimmune encephalomyelitis by MIP-1alpha and MCP-1 naked DNA vaccines. 1044 Nov 64

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.
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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.
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PMID:Alterations in cytokine but not chemokine mRNA expression during three distinct Theiler's virus infections. 1068 11


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