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)

Innate immune cells may regulate adaptive immunity by balancing different lineages of T cells and providing negative costimulation. In addition, CD11b(+)Gr-1(+) myeloid-derived suppressor cells have been described in tumor, parasite infection, and severe trauma models. In this study, we observe that splenic CD11b(+) cells markedly increase after experimental autoimmune encephalomyelitis (EAE) immunization, and they suppress T cell proliferation in vitro. Although >80% of CD11b(+) cells express varying levels of Gr-1, only a small population of CD11b(+)Ly-6C(high) inflammatory monocytes (IMC) can efficiently suppress T cell proliferation and induce T cell apoptosis through the production of NO. IFN-gamma produced by activated T cells is essential to induce IMC suppressive function. EAE immunization increases the frequencies of IMC in the bone marrow, spleen, and blood, but not in the lymph nodes. At the peak of EAE, IMC represent approximately 30% of inflammatory cells in the CNS. IMC express F4/80 and CD93 but not CD31, suggesting that they are immature monocytes. Furthermore, IMC have the plasticity to up-regulate NO synthase 2 or arginase 1 expression upon different cytokine treatments. These findings indicate that CD11b(+)Ly-6C(high) IMC induced during EAE priming are powerful suppressors of activated T cells. Further understanding of suppressive monocytes in autoimmune disease models may have important clinical implications for human autoimmune diseases.
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PMID:CD11b+Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis. 1791 8

Hyperforin (Hyp) is an active compound contained in the extract of Hypericum perforatum, well known for its antidepressant activity. However, Hyp has been found to possess several other biological properties, including inhibitory effects on tumor invasion, angiogenesis, and inflammation. In this paper, we show that treatment with Hyp inhibited IFN-gamma production, with down-regulation of T-box (T-bet; marker of Th1 gene expression) and up-regulation of GATA-3 (marker gene of Th2) on IL-2/PHA-activated T cells. In parallel, we showed a strong down-regulation of the chemokine receptor CXCR3 expression on activated T cells. The latter effect and the down-modulation of matrix metalloproteinase 9 expression may eventually lead to the inhibition of migratory capability and matrix traversal toward the chemoattractant CXCL10 by activated lymphocytes that we observed in vitro. The effect of Hyp was thus evaluated on an animal model of experimental allergic encephalomyelitis (EAE), a classic, Th1-mediated autoimmune disease of the CNS, and we observed that Hyp attenuates the severity of the disease symptoms significantly. Together, these properties qualify Hyp as a putative, therapeutic molecule for the treatment of autoimmune inflammatory disease sustained by Th1 cells, including EAE.
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PMID:Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease. 1794 92

Specialized glia, termed reactive astrocytes, accompany numerous pathologic conditions affecting the central nervous system, including stroke, multiple sclerosis, and neoplasia. To better define this important cell type, we employed high-density microarray gene expression profiling using two in vitro models of reactive gliosis (stimulation with dbcAMP or IL-1beta/IFNgamma). We identified 44 differentially expressed transcripts common to both in vitro models and demonstrated that a subset of these genes are also differentially expressed in response to experimental autoimmune encephalomyelitis and focal cerebral ischemia in vivo. Moreover, this pattern of differential gene expression is not observed in hyperproliferating or neoplastic glia.
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PMID:Expression profiling identifies a molecular signature of reactive astrocytes stimulated by cyclic AMP or proinflammatory cytokines. 1805 18

The possibility to generate and expand tolerogenic dendritic cells (DC) with TGF-beta1 in vitro opens new therapeutic perspectives for the treatment of autoimmune diseases. In the present study, GM-CSF+IL-4 induced the differentiation of DC from adherent peripheral blood mononuclear cells, which had a higher expression of HLA-DR, CD86 and CD1a and the capacity to stimulate T cells. TGF-beta1 alone slightly promoted the generation of antigen presenting cells (APC) with higher expression of CD14, but did not differentiate them into E-cadherin+Langerhans cell (LC)-like DC. TGF-beta1-driven APC exhibited the morphology, phenotypes and functions of tolerogenic immature DC, and had lower capacity to stimulate T cells. In vivo experiment demonstrates that TGF-beta1-treated APC exhibited the therapeutic potential in Lewis rats with experimental autoimmune encephalomyelitis (EAE), followed by increase of IL-10 production in lymph nodes and decrease of inflammatory cells in spinal cords. Most importantly, GM-CSF/IL-4 used in DC preparation abolished the effect of TGF-beta1 to induce tolerogenic APC in vitro and in vivo. The results reveal that the usage of GM-CSF for the generation of tolerogenic DC should not be copied from DC preparation for anti-tumor therapy.
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PMID:The presence of GM-CSF and IL-4 interferes with effect of TGF-beta1 on antigen presenting cells in patients with multiple sclerosis and in rats with experimental autoimmune encephalomyelitis. 1806 Nov 54

Macrophages generally constitute a major component of tumor stroma, and possess either tumor growth promoting or inhibiting capabilities. Classically activated macrophages exert cytotoxicity and produce inflammatory cytokines, which limits tumor growth. By contrast, alternatively activated or M2 macrophages induce tumor progression by stimulating angiogenesis and proliferation. Previously we showed that resident macrophages control metastatic spread of coloncarcinoma cells in liver and peritoneal tumor models. However, it is proposed that newly recruited macrophages develop into tumor-associated M2 macrophages, as they are exposed to a microenvironment that favors alternative activation. Previously we showed that monocyte migration was diminished after flavonoid treatment in an experimental autoimmune encephalomyelitis animal model. In the present study, we investigated the role of newly recruited macrophages in colon carcinoma development, by using the flavonoids rutin and luteolin to reduce monocyte migration into peritoneal tumors. Increased tumor development was observed in animals that were treated with rutin and luteolin. Immunohistochemical analyses showed that the number of ED2(+) resident macrophages was normal in tumors of animals that received rutin and luteolin treatment. However, the number of ED1(+) cells (marker immature macrophages) was reduced, indicating decreased macrophage recruitment. Thus, inhibition of monocyte migration promotes tumor growth, supporting that not only resident, but also newly recruited macrophages limit peritoneal colon carcinoma metastases development.
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PMID:Tumor infiltrating macrophages reduce development of peritoneal colorectal carcinoma metastases. 1818 56

Dendritic cells (DCs) are the most potent antigen-presenting cells (APC) of the immune system, and are critically involved in initiation of immune responses in autoimmune diseases. They can modulate the nature of immune responses to stimulatory or tolerogenic fashion. Previous studies have demonstrated that the administration route of DCs is an important variable in eliciting anti-tumor immunity. In this study we used experimental autoimmune encephalomyelitis (EAE) as an animal model of multiple sclerosis to compare different protocols of DC delivery in autoimmunity or tolerance induction. Dendritic cells were generated from bone marrow cells of C57BL/6 mice by culturing in the presence of GM-CSF and IL-4 for 7 days, followed by 2 days culture with TNF-alpha. The obtained DCs were pulsed in vitro with myelin oligodendrocyte glycoprotein (MOG) peptide and injected (5 x 10(5) cells/mouse) via the intravenous (i.v.), intraperitoneal (i.p.) or subcutaneous (s.c.) route into female C57BL/6 mice. In some instances pertussis toxin was also injected zero and 48 hours after DC injection. After follow up of the mice pretreated in this way for 4 weeks, in the i.v. group in which no clinical signs of EAE occurred, the mice were immunized with MOG peptide for EAE induction via the common method and the results were compared with mice that were not pre-immunized. Only after three s.c. DC injections with pertussis toxin, the mice showed mild clinical signs of EAE, whereas mice given i.v. or i.p. injections with or without pertussis toxin failed to develop EAE after 4 weeks. Induction of EAE via the common method after three injections of TNF-alpha treated DCs, in i.v. injected groups showed no protection from EAE. It seems that several factors influence the tolerance versus immunity induction by DCs. Our results showed that the administration route of DCs is one of the pivotal factors in DC-based induction of autoimmune diseases.
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PMID:Experimental autoimmune encephalomyelitis (EAE) induced by antigen pulsed dendritic cells in the C57BL/6 mouse: influence of injection route. 1825 18

The Pten tumor suppressor gene is critical for normal intrathymic development of T cells; however, its role in mature antigen-activated T cells is less well defined. A genetically crossed mouse line, Pten(fl/fl) GBC, in which Pten gene deletions could be primarily confined to antigen-activated CD8+ T cells, enabled us to evaluate the consequences of Pten loss on the course of experimental autoimmune encephalomyelitis. Compared with Pten(fl/fl) controls, myelin oligodendrocyte glycoprotein (MOG) peptide-immunized Pten(fl/fl) GBC mice developed more severe and protracted disease. This was accompanied by increased spinal cord white matter myelin basic protein depletion and axonal damage, as well as a striking persistence of macrophage and granzyme B-expressing cellular neuroinfiltrates in the chronic phase of the disease. This persistence may be explained by the observation that anti-CD3 activated Pten(fl/fl) GBC T cells were more resistant to proapoptotic stimuli. Consistent with the predicted consequences of Pten loss, purified CD8+ T cells from Pten(fl/fl) GBC mice displayed augmented proliferative responses to anti-T-cell receptor stimulation, and MOG-primed Pten(fl/fl) GBC T cells exhibited a reduced activation threshold to MOG peptide. Pten(fl/fl) GBC mice also developed atypical central nervous system disease, manifested by prominent cervical cord and forebrain involvement. Collectively, our findings indicate that the phosphatidylinositol 3-kinase signaling pathway is an essential regulator of CD8+ T-cell effector function in experimental autoimmune encephalomyelitis.
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PMID:Antigen-induced Pten gene deletion in T cells exacerbates neuropathology in experimental autoimmune encephalomyelitis. 1834 28

A 65-year-old man was admitted to our hospital complaining of diplopia, dysarthria, difficulty in walking and progressive dysesthesia that developed in his left hand and leg. Brain MRI revealed high signal intensity regions on T2-weighted and FLAIR images of the hippocampus and the corpus amygdaloideum. After admission, the patient's neurological symptoms progressed to delirium and dementia with hallucinations. When he eventually developed severe respiratory failure requiring ventilatory support, brain MRI revealed new high signal intensity regions on T2-weighted images of the medulla oblongata and pons. Chest CT scans showed a mass under the aortic arch, and based on subsequent histopathological examination of a transesophageal endoscopic ultrasonography-guided fine needle aspiration biopsy of the tumor, a diagnosis of small cell lung cancer was made. In addition, anti-Hu antibody was found in the patient's serum, leading to a diagnosis of paraneoplastic encephalomyelitis/sensory neuropathy. One course of chemotherapy (carboplatin + etoposide) was administered; however, the protocol was not completed because the patient developed severe pneumonia. Given that neurological symptoms usually precede a diagnosis of malignancy in paraneoplastic neurological syndromes, it is important that these are considered carefully, as they may contribute to early diagnosis and treatment. Here we report a rare case of severe central hypoventilation in paraneoplastic encephalomyelitis/sensory neuropathy.
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PMID:[Paraneoplastic neurological syndrome accompanied by severe central hypoventilation and expression of anti-Hu antibody in a patient with small cell lung cancer]. 1851 96

The antioxidant lipoic acid (LA) treats and prevents the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In an effort to understand the therapeutic potential of LA in MS, we sought to define the cellular mechanisms that mediate the effects of LA on human natural killer (NK) cells, which are important in innate immunity as the first line of defense against invading pathogens and tumor cells. We discovered that LA stimulates cAMP production in NK cells in a dose-dependent manner. Studies using pharmacological inhibitors and receptor transfection experiments indicate that LA stimulates cAMP production via activation of the EP2 and EP4 prostanoid receptors and adenylyl cyclase. In addition, LA suppressed interleukin (IL)-12/IL-18 induced IFNgamma secretion and cytotoxicity in NK cells. These novel findings suggest that LA may inhibit NK cell function via the cAMP signaling pathway.
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PMID:Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells. 1856 16

We have shown recently that cDNA vaccination, using a virtual lymph node, ameliorates experimental allergic encephalomyelitis. Successful cure from mammary tumor requires resolution of local tumor growth and metastases. We have examined whether targeting of CD44 cell surface adhesion molecule by cDNA vaccination plays a role in resolving mammary tumor development. We show here that CD44 cDNA vaccination decreases the tumor mass and metastatic potential in experimental mammary tumor of BALB/c mice. Vaccination of mice, inoculated with the mammary tumors, by cDNA of CD44 variant (CD44v) but not by cDNA of standard CD44, markedly reduced local tumor development and lung metastasis. Concomitantly, transfection of CD44 antisense into a highly metastatic mammary tumor cell line disrupted the CD44 expression of the cells and reduced their ability to establish local tumors as well as metastatic colonies in the lung. Moreover, when CD44v, but not standard CD44 sense cDNA, was transfected into the poorly metastatic cell line, tumor development was markedly enhanced. It is possible therefore that DNA vaccination with a specific CD44v construct could induce an immune resistance to mammary tumor progression.
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PMID:DNA vaccination with CD44 variant isoform reduces mammary tumor local growth and lung metastasis. 1856 32


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