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

---

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

Major histocompatibility class II antigen (Ia) expression is thought to play an important role in the pathogenesis of autoimmune central nervous system (CNS) disease. It has been suggested that Ia expression within the CNS might be sufficient to induce experimental allergic encephalomyelitis (EAE). The expression of Ia antigen in the CNS was studied during the natural course of both acute and chronic relapsing EAE. We found that Ia expression in the CNS starts at a relatively late stage in the course of EAE and persists after the disappearance of the clinical signs. In order to further evaluate the functional significance of Ia expression on glial cells we also studied the effect of intraventricular administration of interferon-gamma. This caused widespread Ia expression within the CNS but no signs of autoimmune CNS disease. Based on these results and data from the literature, the role of local Ia expression in the CNS is reconsidered. In certain circumstances Ia expression may contribute to suppressive rather than enhancing effects on the immune response.
...
PMID:The significance of in-situ Ia antigen expression in the pathogenesis of autoimmune central nervous system disease. 839 14

In an adoptive transfer model of experimental allergic encephalomyelitis, stimulation of lymph node cells with proteolipid protein and recombinant murine interleukin (rmIL)-12 before cell transfer accelerated the onset and exacerbates clinical disease. In vitro stimulation with proteolipid protein in the presence of rmIL-12 was associated with an increase in interferon-gamma-producing cells and a decrease in IL-4-producing cells, indicating a preferential expansion of Th1 effector cells. This was supported by the finding that severe disease with rapid onset could be transferred with as few as 10 x 10(6) rmIL-12-stimulated lymph node cells. Immunohistochemical analysis confirmed that the accelerated onset of disease after in vitro stimulation with rmIL-12 coincided with an acute inflammatory response in the central nervous system. At peak disease, both control and rmIL-12 treatment groups exhibited extensive cellular infiltration with characteristic perivascular cuffing. No notable differences in either the cellular composition or cytokine expression within the lesions were seen between groups. However, the frequency of macrophages that stained positively for inducible nitric oxide synthase was increased in animals challenged with rmIL-12-treated lymph node cells. The results suggest that, in addition to promoting the preferential expansion of interferon-gamma-producing cells by rmIL-12 in vitro, secondary in vivo effects leading to macrophage activation and inducible nitric oxide synthase expression may contribute to the severe and protracted course of central nervous system inflammation in this model.
...
PMID:Adoptive transfer of experimental allergic encephalomyelitis after in vitro treatment with recombinant murine interleukin-12. Preferential expansion of interferon-gamma-producing cells and increased expression of macrophage-associated inducible nitric oxide synthase as immunomodulatory mechanisms. 857

Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously demonstrated that exposure of gut-associated lymphoid tissue to myelin basic protein (MBP) via oral administration suppresses experimental autoimmune encephalomyelitis (EAE). To further study presentation of antigen to the immune system by mucosal surfaces as a method of antigen-driven tolerance, the effect of inhalation of MBP was investigated. MBP was given as an aerosol to Lewis rats on Days -10, -7, -5, and -3 prior to immunization with MBP in Freund's adjuvant and on Days 0, 2, and 4 following immunization. Aerosolization of MBP completely abrogated clinical EAE in 100% of treated rats. Central nervous system inflammation and delayed-type hypersensitivity and antibody responses to MBP were also significantly reduced in aerosol-treated animals. Aerosolization of histone, a basic protein of similar weight and charge as MBP, had no effect. Disease was also suppressed with one aerosol treatment on Day -3 or by administering MBP nasally. Aerosolization was more effective than oral administration of MBP over a wide dose range (0.005-5 mg). Splenic T cells isolated from animals postaerosolization adoptively transferred protection to naive animals immunized with MBP. Aerosolization of MBP to animals with relapsing EAE after recovery from the first attack decreased the severity of a subsequent attack. Aerosol and oral MBP were equally effective at suppressing the in vitro immune response as measured by proliferation and interferon-gamma production. We then tested aerosolization of a different autoantigen in a different disease model and found that aerosolization of type II collagen was effective in suppressing collagen-induced arthritis. Thus, aerosolization of an autoantigen is a potent method to downregulate an experimental T cell-mediated autoimmune disease and suggests that exposure of antigen to lung mucosal surfaces preferentially generates immunologic tolerance.
...
PMID:Antigen-driven peripheral immune tolerance: suppression of experimental autoimmmune encephalomyelitis and collagen-induced arthritis by aerosol administration of myelin basic protein or type II collagen. 866 Aug 45

The expression of cell adhesion molecules (CAMs) in the choroid plexus was studied in normal brain and during experimental autoimmune encephalomyelitis (EAE) in the SJL/J mouse during inflammation induced by intracerebral injection of killed Corynebacterium parvum in the C3H/He mouse. Both ICAM-1 and VCAM-1, but not MAdCAM-1, were constitutively expressed on choroid plexus epithelium but not on the fenestrated capillary endothelial cells within the choroid plexus. During EAE, we observed an up-regulation of ICAM-1 and VCAM-1 and de novo expression of MAdCAM-1 on choroid plexus epithelial cells. In contrast, endothelial cells in the choroid plexus were not induced to express any of the investigated CAMs. In in situ hybridization analysis we demonstrated that ICAM-1, VCAM-1, and MAdCAM-1 were locally synthesized and that the amount of their mRNAs increased in the inflamed choroid plexus. In vitro, primary choroid plexus epithelial cells could be induced to express ICAM-1, VCAM-1, and MAdCAM-1 on their surface after treatment with proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, interferon-gamma, and lipopolysaccharide. To investigate the functional status of the expressed CAMs we performed Stamper-Woodruff binding assays on frozen sections of inflamed and naive brains. ICAM-1, VCAM-1, and MAdCAM-1 expressed in choroid plexus epithelial cells mediated binding of lymphocytes via their known ligands LFA-1 and alpha4-integrin, respectively. The expression of ICAM-1, VCAM-1, and MAdCAM-1 on choroid plexus epithelial cells together with the lack of their expression on the fenestrated choroid plexus endothelium raises the possibility that the epithelial blood-cerebrospinal-fluid barrier plays an important role in the immunosurveillance of the central nervous system.
...
PMID:ICAM-1, VCAM-1, and MAdCAM-1 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro. 866 69

Oral administration of autoantigens can prevent and partially suppress autoimmune diseases in a number of experimental models, Depending on the dose of antigen fed, this approach appears to involve distinct yet reversible and short-lasting mechanisms (anergy/deletion and suppression) and usually requires repeated feeding of large (suppression) to massive (anergy/deletion) amounts of autoantigens to be effective. Most importantly, this approach is relatively less effective in animals already systemically sensitized to the fed antigen, such as in animals already harboring autoreactive T cells and, thus, presumably also in humans suffering from an autoimmune disorder. We have previously shown that feeding a single dose of minute amounts of antigens conjugated to cholera toxin B subunit (CTB) can effectively suppress delayed-type hypersensitivity reactions in systemically immune animals. We now report that feeding small amounts of myelin basic protein (MBP) conjugated to CTB either before or after disease induction protected rats from experimental autoimmune encephalomyelitis. Such treatment was as effective in suppressing interleukin 2 production and proliferative responses of lymph node cells to MBP as treatment involving repeated feeding with much larger (50- to 100-fold) doses of free MBP. Different from the latter treatment, which led to decreased production of interferon-gamma in lymph nodes, low-dose oral CTB-MBP treatment was associated with increased interferon-gamma production. Most importantly, low-dose oral CTB-MBP treatment greatly reduced the level of leukocyte infiltration into spinal cord tissue compared with treatment with repeated feeding of large doses of MBP. These results suggest that the protection from experimental autoimmune encephalomyelitis achieved by feeding CTB-conjugated myelin autoantigen involves immunomodulating mechanisms that are distinct from those implicated by conventional protocols of oral tolerance induction.
...
PMID:Treatment of experimental autoimmune encephalomyelitis by feeding myelin basic protein conjugated to cholera toxin B subunit. 869 68

The mechanism of CD40 ligand (CD40L)-mediated in vivo activation of CD4(+) T cells was examined by investigation of the development of experimental allergic encephalomyelitis (EAE) in CD40L-deficient mice that carried a transgenic T cell receptor specific for myelin basic protein. These mice failed to develop EAE after priming with antigen, and CD4(+) T cells remained quiescent and produced no interferon-gamma (IFN-gamma). T cells were primed to make IFN-gamma and induce EAE by providing these mice with B7.1(+) antigen-presenting cells (APCs). Thus, CD40L is required to induce costimulatory activity on APCs for in vivo activation of CD4(+) T cells to produce IFN-gamma and to evoke autoimmunity.
...
PMID:Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis. 879 92

Microglia, a population of central nervous system (CNS) macrophages, have been demonstrated to support immune accessory and effector functions in the CNS. Numerous studies support the role of microglia in CNS development and pathology, where activation of microglia is consistently noted. The current study investigated microglial immune functions under basal and activation conditions and assessed the ability of interleukin-10 (IL-10), added exogenously or produced by microglia, to down-regulate microglial functions. This report demonstrates that microglia from the adult human brain produce IL-10 following interferon-gamma/lipopolysaccharide activation. Functionally, recombinant human IL-10 down-regulated basal HLA-DR expression by microglia and inhibited, in a dose-dependent response, the ability of microglia to stimulate CD4+ T-cells in antigen presentation assays. These data, together with recent observations of the inhibition of experimental allergic encephalomyelitis (EAE) following IL-10 administration and reduced CNS infection by Listeria monocytogenes after anti-IL-10 treatment, suggest that IL-10 production by microglia may have important immune-regulatory functions in CNS disease and disease models.
...
PMID:IL-10 production by adult human derived microglial cells. 880 89

Experimental autoimmune encephalomyelitis (EAE) in rats is typically a brief and monophasic disease with sparse demyelination. However, inbred DA rats develop a demyelinating, prolonged and relapsing encephalomyelitis after immunization with rat spinal cord in incomplete Freund's adjuvant. This model enables studies of mechanisms related to chronicity and demyelination, two hallmarks of multiple sclerosis (MS). Here we have investigated, in situ, the dynamics of cytokine mRNA expression in the central nervous system (CNS) and peripheral lymphoid organs (lymph node cells and splenocytes) of diseased DA rats. We demonstrate that peripheral lymphoid cells stimulated in vitro with encephalitogenic peptides 69-87 and 87-101 of myelin basic protein responded with high mRNA expression for proinflammatory cytokines; interferon-gamma, interleukin-12 (IL-12), tumour necrosis factors alpha and beta, IL-1 beta and cytolysin. A high expression of mRNA for these proinflammatory cytokines was also observed in the CNS where it was accompanied by classical signs of inflammation such as expression of major histocompatibility complex class I and II, CD4, CD8 and IL-2 receptor. The expression of mRNA for proinflammatory cytokines was remarkably long-lasting in DA rats as compared to LEW rats which display a brief and monophasic EAE. Furthermore, mRNAs for putative immunodownmodulatory cytokines, i.e. transforming growth factor-beta (TGF-beta), IL-10 and IL-4 were almost absent in DA rats, in both the CNS and in vitro stimulated peripheral lymphoid cells, while their levels were elevated in the CNS of LEW rats during the recovery phase. We conclude that the MS-like prolonged and relapsing EAE in DA rats is associated with a prolonged production of proinflammatory cytokines and/or low or absent production of immunodownmodulatory cytokines.
...
PMID:Cytokines in relapsing experimental autoimmune encephalomyelitis in DA rats: persistent mRNA expression of proinflammatory cytokines and absent expression of interleukin-10 and transforming growth factor-beta. 882 81

The pathogenesis of Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is still controversial. Our hypothesis is that primary infection of oligodendrocytes (OLGs) is not a crucial event in the pathogenesis of demyelination in this model. In fact, it has been proposed that myelin may be destroyed, as an innocent bystander, following an antiviral delayed-type hypersensitivity (DTH) response. This hypothesis would not need widespread oligodendroglial infection, because virus present in other cells would be sufficient to trigger a DTH response. The present study demonstrates that cultured OLGs and astrocytes from susceptible strains of mice (SJL and DBA) and immortalized OLGs can be infected with TMEV in vitro. Infection of OLGs, however, is at very low levels and does not result in overt cytolytic effect. In contrast, infection of immortalized OLGs is very efficient and results in clear cytolysis. Because an important characteristic of DTH responses is the liberation of potentially injurious cytokines into adjacent tissues, we also examined the effects of mouse recombinant tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and interferon-gamma (IFN-gamma) on cultured OLGs and immortalized OLGs. We found that TNF-alpha caused immortalized OLG cytotoxicity in a time- and dose-dependent manner. In contrast, no cytotoxicity was observed on primary OLGs with any of the above cytokines. To determine whether functional effects could be demonstrated on primary OLGs by either virus or cytokines, we measured mRNA expression of different myelin proteins in primary and immortalized OLGs exposed to virus or TNF-alpha. Neither the BeAn strain or the GDVII strain of TMEV interfered with myelin protein mRNA expression in primary OLGs, whereas GDVII virus dramatically reduced myelin OLG glycoprotein (MOG) mRNA in immortalized OLGs. Interestingly, although even high concentrations of TNF-alpha (10,000 U/ml) did not produce primary OLG cytotoxicity, they resulted in a significant reduction in mRNA for both myelin basic protein (MBP) and MOG in these cells. TNF-alpha (at 500 U/ml) also specifically reduced MOG mRNA in immortalized OLGs. Because immortalized OLGs are considered to be arrested at an early stage of maturation, our results suggest that immature OLGs are susceptible to both virus- and cytokine-dependent cytotoxicity, whereas mature OLGs are resistant to cytolysis by either TMEV or cytokines. TNF-alpha, however, is capable of reducing mRNA expression of myelin proteins in primary OLGs; therefore, it may participate in the induction of demyelination, as suggested by the DTH-mediated hypothesis.
...
PMID:Effect of Theiler's murine encephalomyelitis virus and cytokines on cultured oligodendrocytes and astrocytes. 887 96

Tumor necrosis factor-alpha (TNF-alpha) has attracted the greatest attention as a major factor in experimental autoimmune encephalomyelitis (EAE) pathogenesis. We compared rats undergoing EAE with manipulated but healthy animals by examining TNF-alpha gene expression in cells recovered from the brain. We used reverse transcriptase-polymerase chain reaction (RT-PCR) as a sensitive assay for detection and Northern blot hybridization as a reliable quantitative assay of TNF-alpha mRNA. TNF-alpha gene expression was consistently detected in rats immunized with myelin basic protein (MBP) emulsified in complete Freund adjuvant (CFA), but not in rats immunized with MBP emulsified in incomplete Freund adjuvant (IFA), which does not induce EAE. Similarly, brain-derived cells from rats injected with cloned encephalitogenic T cells contained increased amounts of TNF-alpha mRNA compared with rats injected with nonencephalitogenic T cell clones similar in antigen specificity and in vitro lymphokine-producing capacity. Considering that the differing pathogenic capacity of MBP-reactive T cells might result from differing patterns of interaction with glia, we examined the impact of T-cell-glia interaction in vitro on cytokine gene expression in both cell types. Glial components were efficient in inducing TNF-alpha expression in T cells; T cells and T-cell-derived cytokines could elicit expression of several lymphokine genes in glial cells. Comparison of RT-PCR and blot hybridization assays, however, suggested that cytokine expression was much more efficient, on a per cell basis, in T cells than in glia. TNF-alpha was shown to have direct cytotoxic effect on glial cells, which was greatly enhanced by small amounts of interferon-gamma (IFN-gamma).
...
PMID:Production of tumor necrosis factor-alpha as a result of glia-T-cell interaction correlates with the pathogenic activity of myelin basic protein-reactive T cells in experimental autoimmune encephalomyelitis. 887


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---