Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protection of guinea pigs from experimental allergic encephalomyelitis (EAE) was attempted using bacterial lipopolysaccharide (LPS) from 4 sources. The ability of these LPS to induce DNA synthesis in guinea pig lymph node (LN) cells in vitro was also investigated. It was found that there existed a good correlation between the capacity of LPS to suppress EAE and their degree of mitogenic activities for LN cells. LPS from Escherichia coli 0111:B4 (Ec-LPS), which was most effective in suppressing EAE and also best inducer of DNA synthesis in LN cells, enhanced the proliferation of cells forming antibody to myelin basic protein (BP) in the regional LN. These results, in addition to the previous report, suggested that at the inductive phase the proliferation of B lymphocytes or their products, antibodies to BP, could inhibit formation of T lymphocytes sensitized to BP, resulting in suppression of EAE. Lipid A but not PS fraction of Ec-LPS showed a protective activity against EAE and a mitogenic activity for LN cells although less so than whole LPS. In addition, Lipid A appeared to exert its mitogenic effect mainly on B rather than on T lymphocytes.
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PMID:Correlation between the capacity of bacterial lipopolysaccharide to supress experimental allergic encephalomyelitis and its mitogenic activity for lymph node cells in guinea pigs. 9 30

In a previous study, we found particular proteases which degrade myelin basic protein (MBP) in a conditioned medium of cultured rat brain microglia. The MBP degrading activity in microglial-conditioned medium (Mic-CM) increased markedly in the presence of plasminogen. By Sephadex G-150 column chromatography, plasminogen-dependent MBP degrading activity was eluted at the position of about 47 kDa and 28 kDa. Furthermore slight plasminogen-dependent protease activity in the presence of fibrin (tissue plasminogen activator activity) was detected at a molecular weight of about 68 kDa. The two molecular forms (47 kDa and 28 kDa) of plasminogen-dependent protease were demonstrated by casein-zymography, and it was suggested that they were urokinase type-plasminogen activators (uPA). This suggestion was confirmed by immunoblotting using anti-uPA antiserum. The unique 28 kDa type was considered to be produced from the 47 kDa form by limited proteolysis. Secretion of PA from microglia was demonstrated by cell zymography. In contrast, significant secretion of plasminogen activator inhibitor could not be detected in the Mic-CM. In addition, lipopolysaccharide significantly decreased the secretion of PA from microglia, while interleukin-1 and basic fibroblast growth factor enhanced the secretion.
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PMID:Microglia isolated from rat brain secrete a urokinase-type plasminogen activator. 137 34

Experimental autoimmune encephalomyelitis (EAE) in the Lewis rat is a self-limited inflammatory process localized to the central nervous system that is induced by the injection of myelin basic protein (MBP) in adjuvant. Oral administration of MBP suppresses EAE, and this suppression is mediated by CD8+ T cells that adoptively transfer protection and suppress both in vitro and in vivo by the release of transforming growth factor (TGF) beta after antigen-specific triggering. Furthermore, oral tolerance to MBP is enhanced by the concomitant oral administration of lipopolysaccharide (LPS). The present study was undertaken to determine whether the disease course in EAE and its suppression by oral tolerization to MBP is associated with distinct patterns of cytokine expression in the target organ. Detailed immunohistology of the brain was performed at the peak of clinical disease (day 14 after immunization) and after recovery (day 18) in control (ovalbumin [OVA]-fed), MBP-fed, and MBP plus LPS-fed animals. Brains from OVA-fed animals at the peak of disease showed perivascular infiltration with activated mononuclear cells which secreted the inflammatory cytokines interleukins (IL) 1, 2, 6, 8, TNF-alpha, and interferon gamma. The inhibitory cytokines TGF-beta and IL-4, and prostaglandin E2 (PGE2) were absent. In MBP orally tolerized animals there was a marked reduction of the perivascular infiltrate and downregulation of all inflammatory cytokines. In addition, there was upregulation of the inhibitory cytokine TGF-beta. In MBP plus LPS orally tolerized animals, in addition to upregulation of TGF-beta and reduction of inflammatory cytokines, there was enhanced expression of IL-4 and PGE2, presumably secondary to activation of an additional population of immunoregulatory cells. In OVA-fed animals that had recovered (day 18), staining for inflammatory cytokines diminished, and there was the appearance of TGF-beta and IL-4. These results suggest that suppression of EAE, either induced by oral tolerization or that which occurs during natural recovery is related to the secretion of inhibitory cytokines or factors that actively suppress the inflammatory process in the target organ.
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PMID:Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain. 138 85

Interactions between rat microglia and oligodendrocytes were examined in vitro in order to characterize the stages of adherence, phagocytosis and cytotoxicity against oligodendrocytes by microglia. Under resting conditions, microglia showed minimal contact with oligodendrocytes and exhibited surface staining of myelin basic protein and myelin debris only; they were not cytotoxic for oligodendrocytes and did not produce tumour necrosis factor (TNF). On activation with either gamma-interferon or lipopolysaccharide and interferon, these cells increased surface binding for myelin basic protein, showed greater contact with living oligodendrocytes and produced TNF in both secreted and cell surface bound forms. Secreted TNF was capable of killing oligodendrocytes but the cell surface bound form did this more efficiently. In the presence of complement, activated microglia showed significant phagocytosis of myelin basic protein which was not obvious in the unactivated cells. These results suggest that activated microglia in the presence of complement are sufficient to kill and phagocytose the oligodendrocyte-myelin complex in vitro.
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PMID:Interactions between oligodendrocytes and microglia. A major role for complement and tumour necrosis factor in oligodendrocyte adherence and killing. 148 53

In the course of studying the secretory products of microglia, we detected protease activity in the conditioned medium. Various proteins (casein, histone, myelin basic protein, and extracellular matrix) were digested. The protease activity was characterized by using purified myelin basic protein as a substrate. Maximal activity was observed at neutral pH levels (7-8), which was different from the optimum pH level of proteolytic activity observed in the cell homogenate. The activity was inhibited approximately 60 and 50% by 1 mM phenylmethylsulfonyl fluoride and 40 microM elastatinal, respectively. In gel filtration, the major activity, which was inhibited in the presence of N-methoxysuccinyl-Ala-Ala-Pro-Val-methyl chloride, eluted at a position corresponding to a molecular mass of approximately 25 kDa. These results suggest that the major protease present in microglial conditioned medium is elastase or an elastase-like protease. This suggestion was confirmed by the finding that the 25-kDa protein band was stained with anti-elastase antiserum by western blotting. De novo synthesis of elastase in microglia was supported by [35S]methionine incorporation. In the presence of lipopolysaccharide, the secretory elastase decreased. These results demonstrate that microglia secrete proteases, one of which was identified as elastase. The significance of this enzyme production in physiological and pathological conditions is discussed.
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PMID:Identification of elastase as a secretory protease from cultured rat microglia. 154 74

Oral administration of myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis (EAE) in Lewis rats immunized with MBP in Freund's adjuvant. The immunomodulator bacterial lipopolysaccharide (LPS) when given orally in conjunction with MBP enhances the protective effects of MBP feeding in EAE. This synergy was achieved only following oral administration of LPS but not following subcutaneous injection. In contrast, subcutaneous administration of LPS abrogated oral tolerance. A synergism between oral LPS and MBP was also demonstrated for antigen-specific suppression of delayed type hypersensitivity (DTH) responses. Antibody responses to MBP were suppressed by oral administration of MBP but not by MBP plus LPS. The lipid A moeity of LPS mimicked the effects of LPS on disease protection and DTH suppression. These data demonstrate that adjuvants can enhance the induction of antigen-specific oral tolerance for suppression of cell-mediated experimental autoimmune responses.
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PMID:Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. III. Synergistic effect of lipopolysaccharide. 170 Jul 38

The macrophage/monocyte procoagulant activity (MPCA) assay, a sensitive and specific in vitro test for cell-mediated immunity, has been used to ascertain the reactivity of MS peripheral blood mononuclear cells (PBM) to copolymer I (Copl), a synthetic peptide analogue of myelin basic protein (MBP) currently being tested as a possible therapeutic agent in multiple sclerosis (MS). Because the suppressive effect of Copl is believed to lie in its possible cross-reactivity with MBP, the reactivity of PBM of MS patients to MBP was also tested. MS patients either at the stable phase of the relapsing/remitting form or with chronic progressive disease were investigated and compared with patients with other diseases and with healthy subjects. The reactivity to Copl was significantly increased in patients with chronic progressive disease but not in stable MS patients or in control subjects. No difference in reactivity to MBP between MS patients and healthy subjects was found regardless of disease status. However, in the control group comprising patients with other diseases, MBP reactivity was significantly elevated. In chronic progressive MS patients, a relationship was found between the response to Copl and that to MBP, supporting the possibility of an immunological cross-reactivity between these two antigens. There was no significant difference in reactivity to the non-specific stimulant, lipopolysaccharide, between the MS and control groups.
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PMID:Cell-mediated immune response to copolymer I in multiple sclerosis measured by the macrophage procoagulant activity assay. 170 4

Adoptive transfer of experimental allergic encephalomyelitis (EAE) is enhanced after in vitro culture of myelin basic protein (BP)-sensitized lymphoid cells with BP. Addition of lipopolysaccharide (LPS) to the culture further augments transfer of EAE to a level 5 times greater than that achieved with cells activated only with BP. Neither the proliferative response of a BP-specific cell line nor the production of IL-2 by BP-sensitized lymphoid cells in response to BP was augmented by the addition of LPS to the culture. Augmentation of EAE was also observed if recipients received simultaneous injections of BP-sensitized lymph node cells (BP/LNC) cultured with BP (BP-activated) and normal spleen cells cultured independently with LPS (LPS/Spl-C). To analyze the effect of contact between these two cell populations in vivo, we mixed the two cell populations in vitro at reduced cell concentrations. When BP-activated BP-LNC were mixed with LPS-Spl-C in vitro, a marked synergistic proliferative response was observed. Irradiation of BP-activated BP/LNC abrogated this synergistic response, whereas irradiation of LPS/Spl-C did not, suggesting that the proliferating population was in the BP/LNC and that the LPS/Spl-C enhanced their proliferation. These results indicate that LPS exerts its effect through BP-nonspecific cells and that these cells enhance transfer of EAE by augmenting the proliferation of the BP-specific cells in vivo after transfer.
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PMID:LPS augments adoptive transfer of experimental allergic encephalomyelitis in the Lewis rat. 248 79

Recently, a colony of Lewis rats has been described which is resistant to experimental allergic encephalomyelitis (EAE). These rats, termed Le-R, are still histocompatible with other Lewis rats. The genetic defect which results in EAE-resistance was shown not to be linked to the RT1.B (Ir) region of the MHC. Myelin basic protein (BP)-sensitization of Le-R rats induces cells capable of mounting a proliferative response to BP in culture but incapable of transferring EAE after culture with BP. The present study demonstrates that the latter deficiency can be overcome either by incorporating lipopolysaccharide (LPS) in the BP-culture medium or by simultaneous transfer of LPS-activated antigen-nonspecific spleen cells with the BP-sensitized cells. The BP-sensitized Le-R cells fail to transfer EAE due to their inability to initiate lesions in the CNS. LPS, working through an antigen-nonspecific cell or cell products, can correct the defect in the Le-R cells such that the antigen-specific cells become capable of initiating CNS lesions which lead to development of clinical EAE.
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PMID:The nature of the defect in experimental allergic encephalomyelitis (EAE)-resistant Lewis (Le-R) rats. 257 12

Bacterial lipopolysaccharide (LPS)-induced protection against experimental allergic encephalomyelitis (EAE) was studied in guinea pigs using chemically modified derivatives. Hydroxylaminolysis or alkaline hydrolysis of LPS, by which ester-linked fatty acids are removed from LPS, resulted in total loss of its mitogenic activity for B lymphocytes, and EAE-suppressive activity was simultaneously reduced. Similar diminished activity was observed in delayed-type skin reactions to myelin basic protein (BP) and anti-BP antibody production detected by passive hemagglutination and enzyme-linked immunosorbent assay (ELISA). These results indicate that the active site of LPS in suppressing EAE is in the lipid portion and that there exists a good correlation between the capacity of LPS to suppress EAE and its mitogenic activity.
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PMID:Further studies on bacterial lipopolysaccharide-induced protection against experimental allergic encephalomyelitis in guinea pigs. Effects of chemical modifications. 618 73


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