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)

Levels of PGE, PGF2 alpha, 6-oxo-PGF1 alpha and thromboxane (TXB2) in spinal cords and cerebellums of guinea pigs at different stages of chronic relapsing allergic encephalomyelitis (CREAE) were compared with those in Freund's adjuvant-treated, age-matched controls. PGE and TXB2 levels were found to be increased in spinal cords during acute and relapse phases of the disease. The number of lesions in the spinal cord was similarly increased in acute and relapse stages. There was, however, no similar correlation between number of lesions and eicosanoid levels in the cerebellum with the clinical stages of the disease based on hind limb paralysis. In the acute phase and remission lesion numbers were low, and high levels, similar to those found in the spinal cord, were only found in the relapse phase. Eicosanoid levels were high in the acute phase and remission, and generally low in relapse. The spinal cord levels of eicosanoids in remission and relapse correlated well with previous data obtained from the CSF of patients with multiple sclerosis.
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PMID:A study of the prostaglandin and thromboxane content of the central nervous tissues with the development of chronic relapsing allergic encephalomyelitis. 345 93

The levels of prostaglandins (PGs) E, F2 alpha and 6-oxo-PGF1 alpha, in spinal cords and cerebellums of guinea pigs were measured during the development of experimental allergic encephalomyelitis (EAE). The earliest change observed was an elevation of PGE in spinal cords, but not cerebellums , 5-7 days post-inoculation (PI) and prior to the appearance of clinical symptoms. PGE content of spinal cords continued to rise until days 12-14 PI when the animals displayed paralytic EAE. In contrast, PGF2 alpha and 6-oxo-PGF1 alpha levels in spinal cords peaked on days 9-11, when the animals exhibited initial clinical signs, but fell to lower values by days 12-14 PI. In cerebellums , the PGE content increased more slowly than in spinal cords, consistent with the lower numbers of mononuclear cell infiltrates, whereas PGF2 alpha and 6-oxo-PGF1 alpha levels remained unaltered. The relationships between the observed changes in prostanoid levels, lesion development and the appearance of clinical symptoms are discussed.
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PMID:A longitudinal study of the prostaglandin content of central nervous system tissues from guinea pigs with acute experimental allergic encephalomyelitis (EAE). 658 39

Prostaglandin (PG) and thromboxane levels were measured in the spinal cords and cerebellums of rats during the induction, disease and recovery periods of experimental allergic encephalomyelitis (EAE). In spinal cords PGE and 6-oxo-PGF1 alpha increased to maximum with the onset of neurological symptoms, 11-12 days after inoculation. However, the levels returned to normal at the height of clinical disease, despite the persistence of inflammatory lesions. After an initial fall, PGF2 alpha increased to normal limits, 11-12 days after inoculation, and remained at this level throughout the experiment. In contrast, the cerebellum content of all the eicosanoids decreased prior to the appearance of clinical EAE. PGF2 alpha and 6-oxo-PGF1 alpha concentrations subsequently increased but the PGE and thromboxane levels remained depressed for the duration of the study. The role of the eicosanoids in modulating the immune response to neuroantigen is discussed together with our recent findings in guinea pigs with acute EAE.
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PMID:Prostaglandin and thromboxane levels in central nervous system tissues from rats during the induction and development of experimental allergic encephalomyelitis (EAE). 660 9

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS). It is an animal model of post-infectious encephalomyelitis and multiple sclerosis (MS). Acute EAE is mediated by macrophages and by T helper 1 (Th1) lymphocytes directed against brain antigens. Inflammation in EAE could potentially be modified by prostaglandins (PG) secreted by blood monocytes (Mo) and brain glial cells. PGE elevates cAMP, which inhibits Mo function and selectively blocks secretion of cytokines by Th1 cells. In the present study, we found that a long-acting PGE1 analogue (LAPGE) inhibited clinical and histological EAE. Indomethacin (INDO) also suppressed active EAE. The combination of INDO plus LAPGE inhibited disease further, possibly by allowing LAPGE to function unopposed by immunostimulatory PG. EAE was suppressed when these agents were administered from the time of immunization or from the onset of clinical disease. The combination of INDO plus LAPGE also inhibited delayed-type hypersensitivity (DTH) reactions to myelin basic protein (MBP), and diminished in vitro lymphocyte responses to mitogens and MBP. PGE analogues and modifiers of arachidonate metabolism block autoimmune responses to brain antigens in vitro and in vivo, and may ameliorate inflammatory and autoimmune diseases of the brain and other organs.
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PMID:Prostaglandins and inhibitors of arachidonate metabolism suppress experimental allergic encephalomyelitis. 752 42

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the brain and spinal cord. It is an animal model of postinfectious encephalomyelitis and multiple sclerosis (MS). In EAE and in MS, monocytes and Th1 lymphocytes penetrate the blood-brain barrier, and the ensuing inflammation causes demyelination and death of oligodendroglia. PGE is a product of blood Mo and of brain glial cells that affects immune regulation. PGE and other cAMP agonists inhibit monocyte function and secretion of cytokines by Th1 cells. However, they have minimal effects on some cytokines secreted by Th2 cells. We hypothesized that eicosenoids would inhibit central nervous system inflammation mediated by Th1 cells. We found that misoprostol, a long-acting PGE1 analog, inhibited clinical and histological signs of moderately severe EAE in Lewis rats. Indomethacin also suppressed EAE and enhanced the LAPGE effect. Both agents suppressed EAE when administered either from the time of immunization or from the onset of clinical disease. The combination of misoprostol and indomethacin inhibited delayed-type hypersensitivity reactions to MBP (a Th1 response). These agents also inhibited in vitro lymphocyte proliferation to mitogens and MBP. Leukotrienes (LKT) elevate intracellular cGMP and amplify immune responses, the opposite of cAMP agonists. We found that LKT synthesis inhibitors blocked EAE, presumably by lowering levels of cGMP in inflammatory cells. Reduction of LKT synthesis enhanced the effects of misoprostol plus indomethacin on EAE. PGE analogs, indomethacin, and inhibitors of LKT synthesis block autoimmune responses to brain antigens in vitro and in vivo. Modification of intracellular cAMP and cGMP levels with these agents may ameliorate inflammatory and autoimmune diseases.
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PMID:Eicosenoids Modify Experimental Allergic Encephalomyelitis. 1185 49

Theiler's murine encephalomyelitis virus (TMEV) causes an acute encephalomyelitis followed by a persistent infection of the central nervous system (CNS) resulting in a chronic inflammation and axonal demyelination in susceptible strains of mice. The pathogenesis of TMEV-induced demyelinating disease remains unknown, but infection of brain glial cells is a critical factor for virus persistence in the CNS. In the present study we investigated the effects of the anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) on the production of inflammatory mediators, such as prostaglandins, after infection of primary astroglial SJL/J murine cultures with TMEV. This infection resulted in a time-dependent transcription of the gene encoding cyclooxygenase-2 (COX-2) and an increased production of prostaglandin E2 (PGE(2)). Both, IL-4 but mainly, IL-10 (1 and 10 ng/ml) decreased the TMEV-induced expression of COX-2 as well as the synthesis of PGE(2). Interestingly, treatment with IL-10 completely abrogated COX-2 induction. The molecular mechanisms involved in the regulation of COX-2 expression by TMEV are unknown, but the effects of anti-inflammatory cytokines may involve the inhibition of the transcription factor nuclear factor B activity and lead to strategies capable of interrupting the inflammatory cascade triggered by TMEV in brain glial cells.
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PMID:Theiler's virus infection induces the expression of cyclooxygenase-2 in murine astrocytes: inhibition by the anti-inflammatory cytokines interleukin-4 and interleukin-10. 1200 31

The effect of 4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101), one of the synthetic retinoids, on collagen-induced arthritis (CIA) in mice and experimental autoimmune encephalomyelitis (EAE) in rats was studied. TAC-101 at doses of 5 and 20 mg/kg clearly inhibited the development of CIA in terms of the swelling of fore- and hind-limbs and bone destruction in knee joints. TAC-101 also suppressed the production of anti-type II collagen (CII) IgG antibody and delayed-type hypersensitivity (DTH) against CII. In addition, TAC-101 delayed the onset and development of EAE but did not affect the maximum symptom of EAE in rats. The elevation of serum antimyelin basic protein (MBP) antibody and DTH to MBP on day 13 clearly suppressed by TAC-101 in EAE rats. Moreover, TAC-101 inhibited the IL-1beta-induced PGE(2) production by MG-63 cells, human osteoblast-like cells, through the suppression of cyclooxygenase II mRNA expression. These findings suggest that TAC-101 inhibits CIA in mice and EAE in rats due to the suppression of immune response to auto-antigen and the production of PGE(2).
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PMID:Effect of synthetic retinoid, TAC-101, on experimental autoimmune disease. 1244

The immunomodulating capacity of heparin led us to test the effect of the synthetic heparin-mimicking and low anticoagulant compound RG-13577 on the course of experimental autoimmune encephalomyelitis (EAE) and central nervous system (CNS) inflammation. EAE was induced in SJL mice by inoculation with whole mouse spinal cord homogenate. RG-13577, delivered intraperitoneally, inhibited the clinical signs of acute EAE and markedly ameliorated inflammation in the spinal cord, primarily by inhibiting heparanase activity in lymphocytes and astrocytes and thus impairing lymphocyte traffic. RG-13577 treatment was effective when started on day of disease induction or day 7 after induction. The low molecular weight heparin, enoxaparin, tested under the same conditions, exerted only a minor insignificant inhibitory effect. RG-13577 also inhibited the tyrosine phosphorylation of several proteins, particularly Erk1 and Erk2 of the MAP kinase signaling pathways associated with inflammation and cell proliferation. RG-13577 blocked the activity of sPLA(2) and inhibited CNS PGE(2) production both in vivo and in vitro.
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PMID:A synthetic heparin-mimicking polyanionic compound inhibits central nervous system inflammation. 1248 85

The arachidonic acid (AA) cascade produces eicosanoids, such as prostaglandins (PGs), that regulate physiological and pathological functions. Although various nonsteroidal anti-inflammatory drugs have been developed, blocking upstream components (cyclooxygenase-1 and -2) of the AA cascade leads to severe side effects, including gastrointestinal ulcers and cardiovascular events, respectively, due to the complexity of the AA cascade. Here, using an AA cascade-targeted lipidomics approach, we report that microsomal PGE synthase 1 (mPGES-1) plays a key role in experimental autoimmune encephalomyelitis (EAE). Eicosanoids (mainly PGD(2)) are produced constitutively in the spinal cord of naive mice. However, in EAE lesions, the PGE(2) pathway is favored and the PGD(2), PGI(2), and 5-lipoxygenase pathways are attenuated. Furthermore, mPGES-1(-/-) mice showed less severe symptoms of EAE and lower production of IL-17 and IFN-gamma than mPGES-1(+/+) mice. Expression of PGE(2) receptors (EP1, EP2, and EP4) was elevated in EAE lesions and correlated with clinical symptoms. Immunohistochemistry on central nervous systems of EAE mice and multiple sclerosis (MS) patients revealed overt expression of mPGES-1 protein in microglia/macrophages. Thus, the mPGES-1-PGE(2)-EPs axis of the AA cascade may exacerbate EAE pathology. Our findings have important implications for the design of therapies for MS.
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PMID:Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis. 1999 78

Diseases caused by immune inflammation, such as rheumatoid arthritis, multiple sclerosis, and Crohn's disease, are intractable diseases to which novel therapeutics are highly demanded. Prostaglandin (PG) E(2) is the most ubiquitously produced PG with various actions. PGE(2) has been traditionally regarded as an immunosuppressant based on its inhibition of T cell activation in vitro. However, in vivo relevance of the immunosuppressant action of PGE(2) has remained obscure. Recently, several groups including ourselves have made unexpected findings that PGE(2) facilitates expansion of the Th17 subset of T helper cells of both human and mouse through elevation of cAMP via PGE receptors EP2 and EP4. We have further found that PGE(2) can induce and not suppress Th1 differentiation under certain conditions, again, through EP2 and EP4. Given the putative roles of these Th subsets in immune diseases such as the above, these findings suggest that, on the contrary to the traditional view, PGE(2) functions as a mediator of immune inflammation. Consistently, administration of an EP4 antagonist could suppress disease progression and development of antigen-specific Th17 cells in mice subjected to experimental allergic encephalomyelitis and contact hypersensitivity. In this perspective, we review these findings and discuss the prospect of EP4 antagonists as immunomodulatory drugs.
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PMID:Prostaglandin E2, an immunoactivator. 2005 52


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