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)

Following a 5-day mixed lymphocyte culture (MLC), C3H/HeJ (H-2k) splenocytes stimulated with DBA/2 (H-2d) gamma-irradiated splenocytes (2000 rads) are specifically cytotoxic in a 4-hr 51Cr-release assay to P815 (H-2d) target cells (62 +/- 2% cytolysis) but not to third-party EL4 (H-2b). However, when the DBA/2 stimulator cells were treated with heat inactivation (45 degrees C for 1 hr), fixed with 1% paraformaldehyde (15 min), or irradiated with ultraviolet-B light (10(4) J/M2), no cell proliferation or cytolytic activity developed in the MLCs. The levels of IL-1, IL-2, and IL-6 from the supernatants of MLC using stimulators undergoing either of the three treatments were markedly decreased compared with that from gamma-irradiated stimulators. Both cell proliferation and specific cytolysis were restored in a dose-dependent fashion by the addition of murine rIL-2 to the MLCs. If the stimulator cells were first activated with 5 micrograms/ml pokeweed mitogen or lipopolysaccharide for 2 days, the subsequent treatment with heat, paraformaldehyde, or UV-B did not significantly affect the development of cytolysis (54-70% cytolysis). Suppressor cells were not detected when cells from the nonresponsive MLCs (2.5 x 10(6) cells) were added to an MLC freshly prepared with gamma-irradiated stimulator cells, or were injected intraperitoneally (50 x 10(6) cells) into naive mice 2 days before recovery and in vitro sensitization of splenocytes. Therefore, modification of the stimulating alloantigen can prevent the release of cytokines that function as an essential second signal in the development of the proliferative response and subsequent cytolysis. The cytokine found to be essential for restoration of this response is IL-2.
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PMID:Restoration of lymphocyte proliferation and CTL generation by murine rIL-2 after treatment of allogeneic stimulator cells by ultraviolet B irradiation, heat, or paraformaldehyde. 182 87

The presence in the body of an antigen species or a bacterial lipopolysaccharide (LPS) has a pleiotropic effect on the immune system activating macrophages, lymphocytes and natural killer (NK) cells. Recently it has been reported that human macrophages not only secrete interleukin-1 (IL-1) but also its inhibitor, called IL-1 receptor antagonist (IL-1ra), structurally similar to IL-1 beta, but with no IL-1-like activity and which binds to the IL-1 receptor. In this study we show that LPS stimulates NK cell activity and IL-1ra potentiates the stimulatory effect of human recombinant interleukin-2 (hrIL-2) on NK cell activity. In addition, we found that hrIL-1ra inhibits DNA synthesis in lymphocyte culture stimulated with phytohaemagglutinin (PHA) (20 micrograms/ml), presumably via IL-1 inhibition. We also found that LPS is a potent stimulator of monokines: IL-6, tumour necrosis factor-alpha (TNF-alpha), and IL-1 beta, as determined by radioimmunoassay method, and interferon-gamma (IFN-gamma), IL-2, TNF-alpha and IL-1 alpha, as determined by ELISA method, in peripheral blood mononuclear cells (PBMC). We used PBMC as effector cells since LPS requires the presence of accessory cells to activate lymphocytes and bind to the HLA-DR molecule on accessory cells. The effect of LPS on PBMC cytotoxicity has been compared with an endotoxin-free extract of Escherichia coli, OM-8990, which did not provoke cytokine production nor did it cause enhancement of NK cell activity. We found that human recombinant IL-1ra potentiates the stimulatory effect of IL-2 on NK cell activity, similar to hrIL-1 beta. The potentiation of IL-2 in stimulating NK cell activity by IL-1ra is not yet understood. Since IL-1ra is a part of the IL-1 family, it may work in a similar fashion to IL-1, which also potentiates IL-2 to enhance NK cell activity but has been shown not to be directly important in tumour cell killing. In addition, hrIL-1ra can amplify the effect of IL-2 on NK activity, possibly by inhibiting the cyclo-oxygenase products, which are immunosuppressive and are generated in antigen-stimulated PBMC cultures. The generation of IFN-gamma by PBMC after treatment with LPS strongly suggests that the enhancement of NK cell activity may be indirectly due to IFN production.
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PMID:Activation of human natural killer cells by lipopolysaccharide and generation of interleukin-1 alpha, beta, tumour necrosis factor and interleukin-6. Effect of IL-1 receptor antagonist. 183 15

Ciprofloxacin (CIP) is a quinolone carboxylic acid derivative with a broad spectrum of antibacterial activity. CIP (0.1-30 micrograms/ml) enhanced DNA synthesis of mouse spleen cells and human peripheral blood lymphocytes (PBL) that had been activated with T cell mitogens or with alloantigens. In addition, CIP increased the amount of IL-2 found in the supernatants of phytohaemagglutinin (PHA)-stimulated human PBL. The presence of CIP in the medium (0.3-10 micrograms/ml) increased the levels of IL-1 found in the culture supernatants of adherence-enriched mouse macrophages, human monocyte/macrophages and a human monocytic cell line stimulated with lipopolysaccharide. In contrast there was no effect of CIP on the release of IL-1 by freshly isolated human monocytes or by cells of the keratinocyte line, A431. CIP alone had no influence on the basal release of IL-2 by NOB-1 cells, a T cell line that responds to IL-1 with an increase in IL-2 synthesis, but, in combination with recombinant IL-1, CIP significantly enhanced the release of IL-2 by these cells. The results of this study suggest that CIP modulates the immune response at two levels--the production of IL-2 by activated T cells and the production of IL-1 by activated monocyte/macrophages. However, CIP did not affect the primary antibody response in vitro or in vivo against sheep erythrocytes and ovalbumin respectively. Thus the enhancing action of ciprofloxacin on the immune system appears to be restricted to T cell function and macrophage/T cell interactions.
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PMID:Ciprofloxacin enhances T cell function by modulating interleukin activities. 183 63

Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins. Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed. In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed. The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS.
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PMID:Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. 187 78

1. Strips of rabbit superior mesenteric artery, precontracted with phenylephrine, relaxed when exposed to human recombinant interleukin-1 (IL-1) of the alpha or beta types. The effect was observed within 10 min, was optimal 32 min after the application of the cytokines and concentration-dependent (12-290 pM). 2. IL-1 alpha and IL-1 beta were equipotent in relaxing the rabbit mesenteric artery. A synthetic fragment corresponding to IL-1 beta 163-171 was approximately one million fold less active than IL-1 beta. The tripeptide Lys-D-Pro-Thr, an analogue of IL-1 beta 193-195, was inactive as an antagonist of IL-1 beta on the preparation. 3. Indomethacin (2.8 microM) prevented or acutely reversed IL-1-induced relaxations in the rabbit mesenteric artery. Purified haemoglobin (10 microM) or the removal of endothelium had no effect on relaxations elicited by IL-1 beta. 4. The preparation exhibited some selectivity for IL-1 as recombinant human tumour necrosis factor-alpha (TNF-alpha), IL-2 or IL-6 failed to influence it. TNF-alpha was not synergistic with a subthreshold concentration of IL-1 beta. 5. Immunoreactive 6-keto-prostaglandin F1 alpha and prostaglandin E2 were increased in the bathing fluid of isolated mesenteric arteries exposed to IL-1 beta as compared to controls. 6. A supernatant of lipopolysaccharide-stimulated human monocytes produced a relaxation of the preparation with a profile similar to that produced with IL-1s and there was a good quantitative agreement between the extent of the relaxation and the enzyme immunoassay measurements of IL-1 alpha and IL-1 beta in the supernatant.Furthermore the relaxation of crude monocyte IL-i was prevented by preincubating with antibodies to IL-l alpha and IL-1 beta. This experiment illustrates the possible use of the preparation for bioassay of IL-1. 7. It is concluded that either form of IL-I relaxes the precontracted rabbit mesenteric artery by a prostaglandin-dependent, nitric oxide-independent mechanism. The model is also useful for distinguishing the mechanism of IL-1-induced hypotension in vivo in rabbits.
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PMID:Human interleukin-1 induces a rapid relaxation of the rabbit isolated mesenteric artery. 188 96

The role of cytokines in the development of acute graft-vs-host disease (GVHD) was investigated in B6AF1 mice that were injected with parental A/J lymphocytes. Splenocytes from GVH mice exhibited an increased capacity to produce interleukin (IL)-1, IL-6, and TNF-a when stimulated in culture with lipopolysaccharide (LPS). This enhanced capacity was diminished following in vivo treatment with immunosuppressive drugs. Concanavalin A-stimulated GVH spleen cells produced significantly lower levels of IL-2 but higher levels of interferon-gamma (IFN-gamma) than did syngeneic spleen cells. Immunosuppressive therapy in vivo increased the capacity of GVH spleen cells to produce IL-2. However, immunosuppressants differed in their effects on IFN-gamma production. Sch 24937 (6-bromo-5-chloro-2-[1-(methylsulfonyl)acetyl] 3-(2-pyridyl)indole) enhanced or had no effect while cyclosporin A consistently decreased the capacity of splenocytes to produce this lymphokine. These results indicate that the capacity of GVH splenocytes for cytokine production can be differentially affected by the actions of some pharmacological agents. The data also indicate that there may be differential regulation of the production of IL-2 and IFN-gamma by the Th1 subset in the GVH spleen.
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PMID:A study of cytokine production in acute graft-vs-host disease. 190 99

Mouse macrophages infected with Trypanosoma cruzi in vitro may be activated to reduce parasite infection by interferon gamma (IFN-gamma). The addition of up to 10,000 units of IFN-gamma however, does not result in a 100% reduction of intracellular parasites. We, therefore, investigated the possibility that macrophages require an additional signal or signals to completely clear T. cruzi infection. Because the combination of IFN-gamma with lipopolysaccharide greatly enhanced macrophages ability to decrease the number of intracellular parasites, the interaction of IFN-gamma with tumor necrosis factor (TNF) was examined. TNF alone and the combination of TNF with IFN-gamma did not have a significant effect on reducing parasite numbers below that obtained with IFN-gamma alone. This was also true for lymphotoxin, a lymphokine similar to TNF in structure and function. The effect of IFN-gamma in combination with a cytokine-rich supernatant containing IL-2, IL-3, IL-4, IL-5, and IFN-gamma on macrophage clearance of the parasite was also examined. The cytokine-rich supernatant alone had no effect on reducing parasite infection of the macrophages; indeed, in some experiments the addition of the supernatant resulted in an increase in the level of parasite infection. However, 1000 units of IFN-gamma combined with the complex cytokine mixture caused a decrease in parasite infection of nearly 100% compared to that of control cultures treated with media alone. To determine which cytokine or cytokines in the supernatant were responsible for this synergistic activity, anti-cytokine antibodies were added to the supernatant prior to its addition with IFN-gamma to the cultures. Anti-IL-4 was the only antibody found to inhibit the synergism of IFN-gamma with the cytokine-rich supernatant. IL-4, however, did not significantly enhance the ability of IFN-gamma to induce macrophage clearance of the parasite, and IL-4 alone caused a slight increase in parasite infection in vitro. These results further define the role that cytokines play in T. cruzi infection of macrophages in vitro and suggest that the interaction of cytokine networks within this system is complex.
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PMID:Trypanosoma cruzi: cytokine effects on macrophage trypanocidal activity. 190 95

The effects of GM-CSF, IL-2, IFN-gamma, TNF-alpha and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-alpha by peripheral blood monocytes were studied. Monocytes were cultured for 20 h in suspension and in serum-free conditions which minimized background stimulation of monokine production. GM-CSF, IL-2 and TNF-alpha directly induced the production of cell-associated IL-1 but little or no IL-1 or TNF-alpha secretion. Combination of GM-CSF with IFN-gamma, IL-2 or TNF-alpha synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-gamma or TNF-alpha also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergistically enhanced TNF-alpha secretion induced by IFN-gamma but not by lipopolysaccharide. GM-CSF did not enhance TNF-alpha secretion induced by IL-2 or TNF-alpha. In contrast, IL-2 synergistically enhanced TNF-alpha secretion induced by IFN-gamma. These results are discussed in relation to cytokine involvement in rheumatoid arthritis.
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PMID:Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-6 on the production of immunoreactive IL-1 and TNF-alpha by human monocytes. 190 83

Interleukin 4 (IL-4) induces the expression of membrane Thy-1 on the vast majority of lipopolysaccharide (LPS)-stimulated normal murine B cells in vitro. This induction is inhibited by interferon-gamma (IFN-gamma). IL-4 and IFN-gamma are required late in culture to effect maximal induction and inhibition of Thy-1 expression by LPS- or LPS + IL-4-stimulated B cells, respectively. IFN-gamma suppresses IL-4-induced Thy-1 expression by inhibiting the induction of steady-state levels of Thy-1-specific mRNA. Three distinct CD4+ Th2 clones, through their release of IL-4, induce B cells to express high levels of Thy-1, by 24 hr, in striking contrast to the 3 days required to induce Thy-1 expression after stimulation with LPS and IL-4. This induction is abrogated by the addition of IFN-gamma. B cells stimulated with three distinct Th1 clones (IFN-gamma- and IL-2-producing) exhibit a modest, non-IL-4-dependent, expression of Thy-1. In contrast to intrinsic expression of Thy-1 by Th2-stimulated B cells. Thy-1 expressed by Th1-stimulated B cells is acquired, having the allotype specificity of the stimulating T cell.
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PMID:Regulation of murine B cell Thy-1 expression by IL-4, IFN-gamma, and CD4+ T cell subsets. 197 79

Vaccination with an inactivated, whole cell, Q fever vaccine (Q-vax) induces lasting antibody conversion and a positive delayed-type hypersensitivity (DTH) skin reaction in about 60% of recipients but a long-lasting positive lymphoproliferative or mitogenic response to C. burnetii antigens with peripheral blood mononuclear cells (PBMC) in 85-95% of subjects. Analysis of the lymphoproliferative response to C. burnetii antigens has now been made by fractionation-reconstitution experiments with PBMC from vaccines, from past infections, and from healthy controls. The major contributor to the response in immune subjects proved to be the T lymphocyte. T cells were stimulated by both the phase I and phase II antigens of two prototype strains of C. burnetii and responses were greatly amplified by addition of IL-2. Similar T lymphocyte stimulation profiles were obtained with the 'Priscilla' strain of C. burnetii which represents a different biotype of Coxiella isolated from Q fever endocarditis; Q-vax is therefore likely to protect against endocarditis strains. Fractionation-reconstitution experiments with T and B cells from vaccines and subjects infected in the past, using various antigenic or haptenic fractions from C. burnetii indicate that protein, non-lipopolysaccharide components of the organism are responsible for the mitogenic response of immune T cells. However, the role of the lipopolysaccharide in the protective immunogen has still to be defined.
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PMID:Analysis of the cells involved in the lymphoproliferative response to Coxiella burnetii antigens. 207 May 64


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