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)

Mouse interferon preparations significantly suppress the in vivo antibody response to sheep red blood cells (SRBC), a thymus-dependent antigen, and to Salmonella typhimurium lipopolysaccharide (LPS), a thymus-independent antigen. It is also possible to effect the late responses of antigen sensitive "memory" cells observed during secondary immunization by administration of interferon prior to primary immunization. The immunosuppressive activity of interferon was time- and dose-dependent. Maximum suppression was produced when animals were given 1.5 times 10-5 units of interferon between 4 and 48 hr before antigenic stimulation. These findings suggested that interferon affects some early event(s) in the process of antibody synthesis which might be related to the general inhibitory effect of interferon on rapidly dividing cells and viral m-RNA translation. In addition, the use of nonadherent spleen cell cultures from interferon-treated mice, immunized in vitro with a thymus-independent antigen, indicated that in this situation the inhibitory effect of interferon was due to an action on B lymphocytes. A variety of soluble "suppressive" factors are secreted by T cells as a consequence of activation by mitogens or specific antigens in vitro. Since T cells are recognized as one of the sources of interferon, it is suggested that interferon should be investigated as a suppressor T cell-produced lymphokine which can regulate B cell expression.
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PMID:Mechanism of the suppressive effect of interferon on antibody synthesis in vivo. 16 63

Endotoxin (lipopolysaccharide, LPS) has been found to act on all three cell types of the immune system, thymus-derived (T-) cells, bone marrow-derived (B-) cells, and macrophages. LPS is mitogenic for B-lymphocytes and activates them to release a chemotactic lymphokine. Macrophage activation appears to be mediated by macrophage-activating factor, another lymphokine released from B-cells. In addition, LPS acts synergistically with phytohemagglutinin to initiate division of purified T-lymphocytes. All these phenomena are mediated by the lipid A moiety of LPS. The role of lymphoid cells in mediating the lethal effects of LPS have also been investigated. The adoptive transfer of spleen cells from LPS-responsive mice (C3H/HeN) to LPS-resistant but histocompatible mice (C3H/HeJ) rendered the LPS-resistant mice significantly more susceptible to LPS-induced lethality. These findings suggest that spleen cells play an essential role in mediating the lethal effects of LPS in vivo.
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PMID:Action of endotoxin on lymphoid cells. 30 90

In vitro assessments were carried out to study some biological aspects of immune lymphocytes producing a new lymphokine, called by the authors Toxoplasma growth inhibitory factor (Toxo-GIF), which inhibits the intracellular multiplication of Toxoplasma gondii within nonimmune mouse macrophages. Concanavalin A and phytohemagglutinin-P were found to induce vigorous production of Toxo-GIF, whereas bacterial lipopolysaccharide did not. In vitro treatment of splenic lymphocytes with rabbit anti-mouse thymocyte serum plus complement abolished almost completely their ability to produce Toxo-GIF. Treatment of splenic lymphocytes with inhibitors of protein synthesis, cycloheximide or puromycin resulted in a remarkable reduction of the ability of sensitized lymphocytes to produce this lymphokine. Thus the production of Toxo-GIF seems to be dependent on the cellular metabolic events of sensitized T-lymphocytes. The significant activity of Toxo-GIF was demonstrable even in the supernate of lymphocyte cultures incubated in serum-free medium and was also evident after immune lymphocytes and homologous antigen were incubated for the relatively short period of 10 h.
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PMID:Studies on production of biologically active substance which inhibits the intracellular multiplication of Toxoplasma within mouse macrophages. 30 17

We studied whether reactions at the lymphocyte membrane receptors for complement, immunoglobulin or mitogens would induce lymphokine production. Human peripheral blood mono-nuclear cells were stimulated by C3- or Fc-receptor reactions and with phytohaemagglutinin (PHA) or lipopolysaccharide (LPS) and cultured for 3 or 4 days. C3- and Fc-receptor reactions were brought about by rosette formation with red cells coated with human complement or antibody. Culture supernatants were assayed for migration inhibitory activity with human leucocytes by the leucocyte-migration-in-agarose test. On the average, no migration inhibitory activity could be detected in cultures stimulated by C3- or Fc-rosette formation, mean migration indices (MI) being 99-2 and 96-1, respectively. Of the mitogens, PHA induced distinct lymphokine synthesis (mean MI 60-2) while the mean MI with LPS varied from 97-9-69-8, depending on the mitogen preparation used and the conditions of culture. We conclude that PHA and LPS are able to activate human lymphocytes into elaboration of migration inhibitory factors whilst reactions at C3- or Fc-receptors fail to do so.
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PMID:Leucocyte migration inhibitory activity in supernatants of cultured human mono-nuclear cells stimulated with mitogens or C3- and Fc-receptor reactions. 32 81

A recent addition to the lymphokine network is human IL-10 (hIL-10). This novel lymphokine has striking homology to BCRF1 protein, the product of a previously uncharacterized open-reading frame in the Epstein-Barr virus (EBV) genome. To date, IL-10 expression has been described in several T clones induced with anti-CD3 and phorbol myristate acetate (PMA), in monocytes stimulated with lipopolysaccharide (LPS), and in murine B-cell lymphomas. We sought to determine whether human B cells express hIL-10 and, if so, its relationship to EBV and to other B-cell lymphokines. We studied 21 EBV-positive B-cell lines derived from patients with acquired immunodeficiency syndrome (AIDS) and Burkitt's lymphoma (n = 6), American Burkitt's (n = 3), African Burkitt's (n = 5), and normal lymphoblastoid cell lines (n = 7), in comparison with seven EBV-negative cell lines. All cell lines were activated with the tumor promoters PMA and teleocidin and were studied by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoadsorbent assay (ELISA). We demonstrated that EBV-positive cell lines derived from patients with American Burkitt's lymphoma, and especially those from patients with AIDS, constitutively express large quantities of hIL-10 by Northern blot analysis and ELISA (range, 3,101 to 25,915 pg/mL), and that both teleocidin and PMA induce hIL-10 in these cell lines. In contrast, six of seven EBV-negative cell lines did not express hIL-10 even by RT-PCR, and hIL-10 was not triggered by PMA or teleocidin. To assure that the 350 bp amplified by PCR was hIL-10 and not BCRF1, we used PCR primers, which do not amplify a fragment from plasmid templates containing BCRF1. Cloning and sequencing of the 350 bp product also demonstrated that B-cell IL-10 is identical to hIL-10 from the T-cell clone B21. Correlation of hIL-10 with other B-cell lymphokines secreted by these B-cell lines demonstrated that hIL-10 secretor cell lines also constitutively secrete or can be induced to secrete IL-6, although to a much lesser amount. Since both lymphokines influence B-cell growth and differentiation, we suggest that hIL-10 may contribute to the polyclonal B-cell activation and hyperglobulinemia seen in AIDS patients. Finally, several reports support the hypothesis that EBV is an important cofactor in the development of human immunodeficiency virus type 1 (HIV-1)-related B-cell lymphomas. Detection of large quantities of hIL-10 in B-cell lines derived from AIDS patients, the close association between EBV and hIL-10 shown in this report, and the ability of BCRF1 to capture hIL-10 activities, make hIL-10/BCRF1 an attractive candidate as a factor causing B-cell growth and immortalization in patients with AIDS and B-cell lymphomas.
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PMID:Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10. 842 93

Lymphokine directed isotype switching is preceded by the induced expression of the corresponding germline Ig heavy chain constant region (CH) gene. This association favors a model in which lymphokine induced germline CH gene expression promotes switch recombination by increasing the accessibility of the switch region to a recombinase(s). An important prediction of this model is that the induction of germline CH RNAs represents increased specific de novo transcription. To test if this prediction is fulfilled by the switch commitment factors, IL-4 and transforming growth factor-beta (TGF-beta), we have utilized a B cell line, 1.29, that switches from IgM to IgE and IgA in vitro. In this cell line, IL-4 and TGF-beta increase germline C epsilon and C alpha RNA levels respectively, predominantly by elevating transcription of these genes. Transcription of germline C epsilon and C alpha genes appears to be independently regulated and is not affected by lipopolysaccharide or IL-5. These results are discussed in the context of the molecular events necessary to commit a B cell to an isotype switch.
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PMID:Transcriptional regulation of the germline immunoglobulin C alpha and C epsilon genes: implications for commitment to an isotype switch. 136 52

The potassium channel activator nicorandil, under evaluation for antianginal management, has been shown to decrease neutrophil respiratory burst. Since our laboratory has demonstrated that reactive oxygen species (ROS) increase tumor necrosis factor (TNF) production, we hypothesized that nicorandil might decrease TNF production from a lipopolysaccharide (LPS) challenge via reduction of respiratory burst. Macrophage viability and TNF production were determined after an 18-hr exposure to 5.0 micrograms/ml LPS and varying concentrations of nicorandil. Nicorandil was not toxic to macrophages below 12 mM (94 +/- 3% viability versus control) and decreased ROS and TNF production. Intracellular superoxide production decreased from 164 +/- 24 OD550 to 99 +/- 6 OD550 with 10 mM nicorandil and extracellular superoxide decreased from 3108 +/- 111 to 1760 +/- 210 nM. Hydrogen peroxide production was also decreased by 10 mM nicorandil. TNF production in response to 5 micrograms/ml LPS decreased from 6.8 +/- 0.6 to 2.7 +/- 0.4 ng/ml with 10 mM nicorandil. Northern and slot blot analyses demonstrate that nicorandil acts at a post-transcriptional site. These data imply that nicorandil decreases macrophage TNF production from an LPS challenge, possibly through a reduction in respiratory burst. Such compounds may prove useful in the treatment of conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion injury, oxygen toxicity, adult respiratory distress syndrome, and septic shock.
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PMID:Alterations in macrophage free radical and tumor necrosis factor production by a potassium channel activator. 153 87

Intracellular replication of the protozoan parasite Trypanosoma cruzi inside macrophages is essential for the production of the disease and the development of the parasite. Two CD4+ T cell lines, A10 and A28, were established from T. cruzi-infected BALB/c mice which specifically proliferated to parasite antigens. The trypanocidal activity of BALB/c macrophages was induced upon culture with the A10, but not with the A28 T cell line. The cell-free supernatant from this A10 line, as well as from immune spleen cells stimulated with specific antigen or concanavalin A, but not from the A28 T cell line also activated the trypanocidal activity of peritoneal macrophages or of the J774 macrophage-like cell line. when the lymphokine content of the supernatants from both cell lines was analyzed, it was found that the A10 T cell line secreted interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin 2, whereas the A28 line did not secrete IFN-gamma upon stimulation. Furthermore, the trypanocidal-inducing ability of A10 supernatant was completely abrogated by neutralizing anti-IFN-gamma antibodies and partially abrogated by neutralizing anti-TNF-alpha antibodies. When recombinant cytokines were added to J774 cells, IFN-gamma was able to induce significant trypanocidal activity whereas TNF-alpha was almost ineffective. However, TNF-alpha or lipopolysaccharide (LPS) showed a synergistic effect with IFN-gamma on macrophage activation. IFN-gamma triggered nitric oxide (NO) synthesis by J774 cells whereas TNF-alpha was almost ineffective. TNF-alpha and LPS were also synergistic with IFN-gamma in the NO production. Both the NO production and the trypanocidal activity in J774 cells induced by T cell supernatants or lymphokine combinations were inhibited by N-monomethyl-L-arginine, a competitive inhibitor of NO synthase activity. A good correlation between the levels of NO production and trypanocidal activity induced by different lymphokine preparations was found. Those results suggest that IFN-gamma and TNF-alpha, secreted by T. cruzi-immune T cells, are involved in the activation of the trypanocidal activity of mouse macrophages through an NO-dependent mechanism.
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PMID:Synergism between tumor necrosis factor-alpha and interferon-gamma on macrophage activation for the killing of intracellular Trypanosoma cruzi through a nitric oxide-dependent mechanism. 153 73

Highly purified natural human interferon-alpha (IFN-alpha) inhibited in a dose-dependent manner the proliferation of human peripheral blood lymphocytes (PBL) stimulated with T-cell mitogen concanavalin A (Con A) or with interleukin-2 (IL-2). Contrary to this inhibitory effect, IFN-alpha at the same concentrations significantly increased proliferation of PBL stimulated with B-cell mitogen bacterial lipopolysaccharide (LPS) or with IL-3, and even spontaneous proliferation of PBL was enhanced by IFN-alpha. Proliferation of Con A-stimulated PBL depleted of CD8+ cells was sensitive to the inhibitory action of IFN-alpha, while proliferation of the Con A-stimulated CD4+ cell-depleted PBL was not affected by IFN-alpha. The inhibitory effect of IFN-alpha on PBL proliferation was due to neither inhibition of IL-2 receptor (IL-2R) expression, activation of suppressor cells, nor inhibition of lymphokine production. Rather, IFN-alpha augmented production of IL-1 and IL-2 by PBL. These results show that the suppressive effect of natural IFN-alpha on Con A-induced proliferation of PBL is due to a direct growth-inhibitory effect on CD4+ T cells, and that IFN-alpha simultaneously augments production of lymphokines. This could in turn lead to the increased proliferation of IFN-alpha-resistant cell populations.
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PMID:Inhibitory versus stimulatory effects of natural human interferon-alpha on proliferation of lymphocyte subpopulations. 153 94

Pseudomonas aeruginosa is a dominant pathogen in infection in cystic fibrosis. This bacterium is thought to play a major role in the chronic bronchial infection-induced pathophysiology. Our data showed that whole formalin-fixed heat-killed P. aeruginosa was mitogenic for human lymphocytes and induced production of substantial amounts of tumor necrosis factor alpha (TNF) in peripheral blood mononuclear leukocytes in cultures. Significant amounts of TNF were produced at 10(3) bacteria per 2 x 10(5) mononuclear leukocytes. Treatment of P. aeruginosa with polymixin B did not affect its ability to stimulate TNF production, suggesting that bacterial lipopolysaccharide is not involved. P. aeruginosa, however, did not stimulate production of the T-cell lymphokine lymphotoxin (TNF beta). Exotoxin A, considered to be an important virulence factor produced by P. aeruginosa, did not stimulate either lymphoproliferation or production of TNF. In fact, this toxin, at nontoxic concentrations, was found to depress lymphoproliferation induced by phytohemagglutinin and Staphylococcus aureus and decreased production of TNF, lymphotoxin, and gamma interferon in either lymphocytes or macrophages. This toxin similarly inhibited the production of interleukin-1 beta (IL-1 beta) and IL-1 alpha, but for the inhibition of the latter, 25-fold-less toxin was required than for inhibition of the former. Inhibition of production of TNF was as sensitive as the IL-1 alpha to exotoxin A. The effects of exotoxin A on lymphoproliferation and cytokine production could be neutralized by the addition of anti-exotoxin A antibodies. These results suggest that two mechanisms by which P. aeruginosa could contribute to the chronic bronchial infection-induced pathophysiology are the nonspecific stimulation of TNF and IL-1 and the release of exotoxin A, a toxin which depresses immune responses.
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PMID:Induction of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by Pseudomonas aeruginosa and exotoxin A-induced suppression of lymphoproliferation and TNF, lymphotoxin, gamma interferon, and IL-1 production in human leukocytes. 163 87


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