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)

The immunotoxicity of the glycol ether 2-methoxyethanol (ME) was evaluated in adult Fischer 344 rats using a variety of in vitro and in vivo immune function assays. In the first phase of this study, male rats were dosed by oral gavage with ME in water, at dosages ranging from 50 to 200 mg/kg/day, for 10 consecutive days. Decreases in thymus weights were observed at dosages of 50-200 mg/kg/day in the absence of decreased body weights. Lymphoproliferative (LP) responses to concanavalin A and phytohemagglutinin were reduced at 50-200 mg/kg/day while pokeweed mitogen and Salmonella typhimurium mitogen responses were reduced at 200 mg/kg/day. No alterations were observed in natural killer cell activity, mixed lymphocyte reaction, or cytotoxic T lymphocyte responses. The frequency of W3/25-positive splenocytes was reduced in rats dosed at 200 mg/kg/day. Interleukin-2 production was reduced in splenocytes from rats exposed to all dosages of ME. The plaque-forming cell (PFC) response to sheep red blood cells was enhanced in rats dosed at 50 mg/kg/day. However, the PFC response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was suppressed at all dosages. Similarly, the PFC response to TNP-LPS was suppressed in adult female rats dosed with ME. A reduction in the expulsion of adult worms was observed in rats dosed at 200 mg/kg/day that were infected with Trichinella spiralis. A number of male reproductive parameters were also evaluated in rats dosed with ME over 10 days. A significant reduction in testicular weight was observed in rats dosed at 200 mg/kg/day. In the second phase of this study, the PFC response to TNP-LPS was employed to assess the role that metabolism of ME to 2-methoxyacetic acid (MAA) plays in the immunotoxicity of this glycol ether. Ten-day oral dosing with MAA resulted in the inhibition of the PFC response to TNP-LPS at dosages of 50-200 mg/kg/day. Concomitant exposure of rats to ME and the alcohol dehydrogenase inhibitor 4-methylpyrazole blocked ME-induced suppression of this PFC response. Attempts to ameliorate ME-induced suppression of the PFC response with serine, which has been shown to reverse ME-induced developmental and reproductive toxicity, were unsuccessful. These results suggest that the immune system may be more sensitive than the reproductive system to the toxic effects of ME. Furthermore, it appears that MAA is the proximate toxicant for ME-induced alterations in the immune system, as has been demonstrated for ME-induced reproductive and developmental toxicity.
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PMID:Immunotoxicity of 2-methoxyethanol following oral administration in Fischer 344 rats. 185 47

Exposure to ethanol in utero results in changes in the offspring's developing immune system, including thymus lymphocyte subpopulation shifts and functional lymphocyte changes that persist in adult animals. The present study was designed to define further the extent of changes in the immune system that result from fetal ethanol exposure and to compare effects in male and female offspring. In adulthood, male and female offspring from Sprague-Dawley dams fed an ethanol-containing liquid diet (alcohol, A), an isocaloric liquid control diet (pair-fed, PF), or laboratory chow and water (control, C) during pregnancy were tested for several measures of immune competency. Prenatal ethanol exposure differentially affected male and female offspring. Fetal ethanol-exposed males exhibited a decrease in thymocyte number as well as a decreased splenic lymphocyte proliferative response to the T-cell mitogen, concanavalin A (Con A), with a concomitant decrease in recoverable blast cells, when compared with PF and C males. Further, the defect in T-cell proliferation of A males was not due to an inability to produce the critical growth factor, interleukin-2 (IL-2), but to an inability of lymphoblasts to utilize exogenous IL-2. Fetal ethanol-exposed females showed some suggestion of lower thymocyte counts and decreased splenic T-cell proliferative responses to Con A compared to PF and C females. For most of the immune measures, however, no significant differences occurred among A, PF, and C females. In utero ethanol exposure did not significantly alter spleen cell counts or IL-2 production, splenic B-cell proliferation to bacterial lipopolysaccharide (LPS), or thymocyte response to IL-2 in animals of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppression of immune responsiveness: sex differences in prenatal ethanol effects. 187 39

The present study was designed to examine the effect of physical exercise on production of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). Ten young, healthy volunteers underwent 60-min bicycle exercise at 75% of maximal oxygen uptake (VO2max). Blood samples were collected before and during the last minutes of exercise, as well as 2 h and 24 h later. Blood mononuclear cells (BMNC) were stimulated in vitro with either bacterial lipopolysaccharide or phytohaemagglutinin, and the supernatants were tested for the above-mentioned cytokines using bioassays as well as ELISA techniques. The production of IL-6 increased significantly 2 h after exercise, furthermore the production of IL-1 alpha and IL-1 beta was enhanced, although only borderline significant. TNF-alpha, IL-2 and IFN-gamma did not fluctuate in relation to exercise. The increased amounts of IL-1 and IL-6 in the supernatants generated from a fixed number of BMNC are most likely explained by the increased percentage and absolute number of blood monocytes 2 h after exercise. IL-2 and IFN-gamma are mainly produced by CD4+ and CD16+ cells. During exercise the CD4+ subset decreases, while the CD16+ subset increases. The finding of unchanged production of IL-2 and IFN-gamma was therefore expected.
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PMID:Effect of physical exercise on in vitro production of interleukin 1, interleukin 6, tumour necrosis factor-alpha, interleukin 2 and interferon-gamma. 190 58

Immune regulation during syphilitic infection is extremely complex. This paper presents findings on the early events of T-cell activation following testicular infection in rabbits. Treponema pallidum was preincubated for 24 h with nonadherent spleen cells. After being washed to remove the organisms, these spleen cells were either stimulated with concanavalin A (ConA) to induce interleukin-2 (IL-2), or added to adherent cells that were then stimulated with lipopolysaccharide to induce IL-1. Preincubation with the treponemes up-regulated nonadherent cell functions. These sensitized cells increased their IL-2 production and augmented macrophage IL-1 synthesis. In sharp contrast, if this preincubation step was omitted, down-regulation was apparent. When T. pallidum was directly incubated with nonadherent cells in the presence of ConA, reduced levels of IL-2 were detected. Nonadherent cells from infected rabbits secreted soluble suppressive factors after 48 h of in vitro incubation; these factors inhibited ConA-induced IL-2 generation as well as ConA-induced lymphocyte proliferation. At least some of this suppressive activity was attributed to transforming growth factor. In addition, when T lymphocytes were depleted, less suppression was detected. Treponemes also inhibited ConA-induced T-cell proliferation, and monophosphoryl lipid A reversed this inhibitory effect. Since monophosphoryl lipid A neutralizes T-suppressor activity, these findings further suggest a role for T-suppressor activity during syphilitic infection. Finally, T. pallidum directly stimulated IL-2 synthesis when coincubated with phorbol myristate acetate. This agent reverses the prostaglandin E2 blockage of T-helper cell protein kinase C, a necessary second messenger signal for IL-2 synthesis. In summary, T-cell functions are extremely complex and represent a composite of both stimulation and down-regulation, which occur concurrently but to different degrees.
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PMID:Splenic T-lymphocyte functions during early syphilitic infection are complex. 193 75

Gamma interferon (gamma-IFN), lipopolysaccharide (LPS)-gamma or interleukin-2 (IL-2)-induced tumor necrosis factor alpha (TNF alpha) production by both macrophages and peripheral blood mononuclear cells (PBMC), was increased in the presence of neopterin. Addition of neopterin caused an increased level of TNF alpha, but did not affect the kinetics of the TNF alpha production, which showed peak levels of cytotoxic activity 4 h after stimulatory treatment. Using anticytokine antibodies, we concluded that the neopterin effect was mainly gamma-IFN mediated, and only slightly affected by anti IL-2 receptor antibodies. The neopterin augmented TNF alpha production can be attributed to an immunological role for neopterin in the enhancement of cell-mediated immune (CMI) response.
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PMID:Neopterin augmentation of tumor necrosis factor production. 195 36

To assess the value of feline immunodeficiency virus (FIV) infection as a model for human immunodeficiency virus (HIV) infection in man, we studied the impairment of certain immunological functions following natural or experimental FIV infection. Proliferative responses of peripheral blood mononuclear cells (PBMC) from symptomatic and asymptomatic cats after naturally or experimentally acquired FIV infection, induced by activation with the mitogens concanavalin A, pokeweed mitogen, or lipopolysaccharide or by stimulation with human interleukin-2 (IL-2), were significantly lower than the proliferative responses found with PBMC from noninfected control cats. Also IL-2 production levels of mitogen-activated PBMC from naturally infected symptomatic cats were significantly reduced. These data confirm that the pathogenesis of FIV infection in the cat, like HIV infection in man, is characterized by a serious malfunction of the immune system.
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PMID:Feline immunodeficiency virus (FIV) infection in the cat as a model for HIV infection in man: FIV-induced impairment of immune function. 196 59

Pyocyanine, a pigment produced by Pseudomonas aeruginosa, has dual dose-dependent stimulatory as well as inhibitory effects on immune responses in vitro as measured by DNA synthesis of human T and B lymphocytes, interleukin-2 (IL-2) production by human T lymphocytes, immunoglobulin production by human B lymphocytes, and monokine production by human monocytes. In general, stimulatory activity was found at low concentrations of pyocyanine, whereas high concentrations of the pigment resulted in an inhibition of responses. At a pyocyanine concentration of 0.1 micrograms/ml or less the proliferation of T and B lymphocytes was enhanced, but at 0.5 micrograms/ml it was suppressed. IL-2 production by T lymphocytes was enhanced at concentrations up to 0.5 micrograms/ml but totally inhibited at 1.0 micrograms/ml. The differentiation of B lymphocytes to become immunoglobulin-producing cells was also enhanced in the presence of low doses of pyocyanine, whereas secretion of immunoglobulin by B lymphocytes was suppressed at all concentrations of pyocyanine. In contrast to the dual effects of pyocyanine on lymphocyte response, lipopolysaccharide-induced IL-1 and tumor necrosis factor release by monocytes was markedly enhanced by low as well as high concentrations of pyocyanine. From these results we conclude that this property of pyocyanine may lead to suppression of specific defense mechanisms and enhance harmful inflammatory reactions of the host during infection with Pseudomonas aeruginosa.
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PMID:Inhibitory and stimulatory effects of Pseudomonas aeruginosa pyocyanine on human T and B lymphocytes and human monocytes. 210 95

Human T cell hybridomas were constructed by somatic cell fusion in order to dissect molecular heterogeneity of human macrophage activating-factors (MAF). Two stable human hybridoma supernatants contained MAF activity capable of inducing human monocytes tumoricidal without the help of bacterial lipopolysaccharide (LPS). These supernatants in the presence of LPS could also render mouse macrophages tumoricidal. In contrast, recombinant and natural human interferon-gamma (Hu-IFN-gamma) activated human monocytes, but not mouse peritoneal macrophages. The supernatants from the two clones could neither support the growth of human-granulocyte-macrophage colony stimulating factor/human-interleukin-4-dependent (Hu-GM-CSF/Hu-IL-4) cell lines, such as AML 193 and TALL-101, nor stimulate the proliferation of human-interleukin-2-dependent human cell line and lectin-stimulated lymphoblast, which are responsive to human-interleukin-2 and human-interleukin-4. Rabbit or murine antibodies against human-interferon-gamma (Hu-IFN), human-granulocyte-macrophage colony stimulating factor, human interleukin-1 alpha, human-interleukin-1 beta, human-interleukin-6, human-tumour necrosis factor (Hu-TNF), human-lymphotoxin and human-macrophage migration inhibitory factor (Hu-MIF) could not absorb MAF activity. MAF activity in the hybridoma supernatants is associated with the two polypeptides of molecular weights of 70,000-80,000 and 20,000-30,000 daltons, as determined by gel filtration. These results indicate decisively that novel MAF molecule(s) is secreted by human T cell hybridomas.
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PMID:Constitutive production of novel macrophage-activating factor(s) by human T cell hybridomas. 212 37

The effect of lipopolysaccharide, muramyl dipeptide, and a combination of these agents in vitro on the production of tumour necrosis factor (TNF) by human peripheral blood mononuclear cells (PBMC; monocytes and lymphocytes) and on the sensitivity of these cells to recombinant interleukin-2 (IL-2) was studied. Both lipopolysaccharide and muramyl dipeptide, alone and combined, induced the production of TNF alpha by blood monocytes and lymphocytes, although the T-cells made only a very small contribution to the TNF produced by the lymphocyte fraction, most being produced by the B-cells. The B-lymphocytes and monocytes also spontaneously produced TNF alpha. Pretreatment of the mononuclear cells with a combination of lipopolysaccharide and muramyl dipeptide, but not with each preparation separately, led to enhancement of the proliferative response of these cells to recombinant IL-2. Incubation of mononuclear cells with muramyl dipeptide, muramyl dipeptide plus lipopolysaccharide, and to a lesser extent with lipopolysaccharide alone led to the generation of more-active lymphokine-activated killer cells in the presence of IL-2 than when IL-2 was used alone. The resultant lymphokine-activated killer cells lysed both human and murine tumour target cells.
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PMID:Enhancement of tumour necrosis factor production and sensitivity to interleukin-2 of human peripheral blood mononuclear cells stimulated by lipopolysaccharide and muramyl dipeptide in vitro. 213 69

Proliferative responses to mitogens were determined by using peripheral blood mononuclear cells from women with active trichomoniasis, with serological evidence of past infection with Trichomonas vaginalis, and with no evidence of current or past infection. Even after the human immunodeficiency virus antibody status of the patients was taken into account, cells from women with active trichomoniasis showed reduced responses to phytohemagglutinin, concanavalin A, pokeweed mitogen, and bacterial lipopolysaccharide. Similar findings were obtained by using spleen cells from mice inoculated subcutaneously with live trichomonads. Reduction in proliferative responses by these cells could be detected 3 days after inoculation. There was some evidence to suggest that more-pathogenic strains of the parasite induced a greater degree of immunosuppression. The responses of spleen cells from mice inoculated with trichomonad-free culture supernatants were within normal limits, indicating that live trichomonads were needed to induce suppression. Support for this was gained from studies with cells from women who were treated successfully. Cells from these women rapidly regained normal lymphoproliferative function. Interleukin-2 (IL-2) production by spleen cells from infected mice was determined from measurements of mitochondrial activity in an IL-2-dependent T-cell line following incubation with stimulated spleen cell culture supernatants. These tests demonstrated lower IL-2 activity in supernatants from cell cultures from infected mice than in those from uninfected mice. The reduction in IL-2 activity did not, however, appear to correlate with the degree of reduction of mitogen-induced lymphoproliferation. Suppression of T-cell-mediated immunity may be one of the mechanisms by which T. vaginalis is able to evade host responses to infection.
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PMID:Reduced lymphocyte responses to mitogens in natural and experimental trichomoniasis. 222 26


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