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 immunomodulatory hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to suppress T-cell proliferation and interleukin-2 synthesis as well as B-cell immunoglobulin synthesis, while stimulating many macrophage functions. We have previously shown increased synthesis of interleukin-1 beta in lipopolysaccharide (LPS)-stimulated U937 cells after pretreatment with 10 nmol/L 1,25-(OH)2D3. We now show that 1,25-(OH)2D3 also primes the increase in U937 cell tumor necrosis factor (TNF)-alpha-accumulated mRNA after activation with LPS; 50% effective concentration (EC50) for the LPS-induced expression of TNF-alpha mRNA was decreased by two orders of magnitude after incubation with 10 nmol/L 1,25-(OH)2D3. Pretreatment of U937 cells with 10 nmol/L 1,25-(OH)2D3 also increased subsequent LPS-induced TNF-alpha mRNA expression by twofold and cell-associated TNF protein levels by more than ninefold. This potentiation was steroid-specific for 1,25-(OH)2D3 because dexamethasone inhibited TNF-alpha mRNA. The potentiation required prior exposure to 1,25-(OH)2D3 for more than 6 hours and was clearly seen after 12 hours. The finding that the sensitivity of the U937 cell monokine response to LPS was dramatically increased by 1,25-(OH)2D3 and the delayed effect on the LPS-stimulated TNF-alpha gene transcript levels indicated that 1,25-(OH)2D3 may be altering the expression of a protein(s) in the U937 cell LPS-signal transduction pathway. In fact, 1,25-(OH)2D3 induced expression of the mRNA for CD14, the high affinity, cell-surface glycoprotein receptor for LPS, which could account for the enhancement of LPS-stimulated monokine gene expression by 1,25-(OH)2D3. Thus, local monokine gene expression may be regulated by both the amount and the temporal entry of the vitamin D hormone and activator(s) into the inflammatory microenvironment.
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PMID:Potentiation of lipopolysaccharide-induced tumor necrosis factor-alpha expression by 1,25-dihydroxyvitamin D3. 145 Apr 7

Culture supernatants from lipopolysaccharide (LPS)-treated murine microglial cells were found to markedly induce the expression of human immunodeficiency virus (HIV)-1 in the chronically infected human promonocytic cell line U1 as detected by measurements of HIV-1 p24 antigen release into U1 culture supernatants. Antibody to tumor necrosis factor (TNF)-alpha had an inhibitory effect on the induction of virus by microglial cell supernatants. Also, treatment of microglia with pentoxifylline, an inhibitor of TNF-alpha production, resulted in suppressed amounts of TNF in the supernatants of LPS-treated microglia and in a reduced stimulatory capacity of these supernatants on HIV-1 expression in U1 cells. These findings support the concept that TNF-alpha production by glial cells plays a pathogenetic role in HIV-1-associated brain disease by promoting the expression of the virus in infected cells.
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PMID:Microglial cell upregulation of HIV-1 expression in the chronically infected promonocytic cell line U1: the role of tumor necrosis factor-alpha. 146 95

1. An injection of D-galactosamine (GalN) into mice together with a lipopolysaccharide (LPS or endotoxin), interleukin-1 (IL-1) or tumour necrosis factor (TNF), sensitized the mice and induced fulminant hepatitis with severe congestion resulting in rapid death. Since LPS and these cytokines induce ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) in the liver and spleen of mice, the effects of GalN on the induction of ODC and HDC in these organs were examined. 2. The induction of ODC by LPS, IL-1 or TNF was suppressed by GalN in the liver, and this suppression preceded the hepatic congestion. There was good agreement between the degree of hepatic congestion and the suppression of ODC induction by various amounts of GalN. The induction of ODC in the spleen was suppressed only at the highest dose of GalN examined. 3. GalN is known to deplete uridine 5'-triphosphate (UTP), resulting in the suppression of RNA and protein synthesis. An injection of uridine, the precursor of UTP, diminished the GalN-induced suppression of ODC induction by LPS and prevented the hepatic congestion and death. 4. LPS-pretreatment before injection of LPS plus GalN prevented the suppression of ODC activity and prevented the hepatic congestion and death. 5. An injection of putrescine, the product of ODC, prolonged survival time and delayed the development of hepatic congestion. However, injection of an ODC inhibitor into the mice given LPS did not produce hepatic congestion. 6. The induction of HDC in the liver by LPS, IL-1 or TNF was not suppressed by GalN and, at high doses, the response to LPS was enhanced. An inhibitor of HDC neither prevented the hepatic congestion nor enhanced the protective effect of putrescine.7. Although GalN in combination with IL-la induced a markedly higher HDC activity than was observed when it was combined with TNFa, and suppressed the induction of ODC, the former combination at the doses used did not produce hepatic congestion or death. However, the sensitization to TNFa by GalN was markedly potentiated by IL-la.8. These results suggest that suppression of the induction of ODC by GalN may be one cause of the sensitization to LPS, IL-1 or TNF, and that the induction of HDC, i.e. histamine formation, may not be involved in this sensitization.9. These results are consistent with the hypothesis that both IL-1 and TNF are involved in the sensitization to LPS.
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PMID:Ornithine and histidine decarboxylase activities in mice sensitized to endotoxin, interleukin-1 or tumour necrosis factor by D-galactosamine. 147 81

When lipopolysaccharide was administered to mice that had been injected with heat-killed Propionibacterium acnes, most of them died of massive liver necrosis. Previously, we demonstrated that a soluble hepatocytotoxic factor released by liver adherent cells fully activated by both P. acnes and lipopolysaccharide was attributable to the late stage of this severe liver injury. In this report, we focused on the hepatocytolysis by these liver adherent cells in a cell-cell interaction manner. Shortly after stimulation with lipopolysaccharide, the P. acnes-elicited liver adherent cells almost completely killed the hepatocytes prepared from both normal syngeneic mice and P. acnes-treated ones. Since P. acnes-elicited liver adherent cells also proved to produce various kinds of cytokines in a short time, the role of cytokines in this liver injury was analyzed. Only TNF-alpha enabled the P. acnes-elicited liver adherent cells to kill hepatocytes prepared from the same mice, but none from the normal ones. These results suggest that the liver adherent cells accumulated and partly stimulated by P. acnes-treatment might rapidly lyse the autologous hepatocytes once triggered by lipopolysaccharide and that the TNF-alpha these liver adherent cells produced might upregulate their own hepatocytotoxic ability.
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PMID:Importance of direct hepatocytolysis by liver macrophages in experimental fulminant hepatitis. 148 70

Glucocorticoid steroids provide considerable protection against the systemic toxicity of tumor necrosis factor-alpha (TNF-alpha, cachexin). In animal experiments RU 38486 (mifepristone), a steroid antagonist, increased the synthesis of TNF and sensitized the animals to the cytotoxic action of TNF. As compared to the control and methylprednisolone-treated groups, mifepristone significantly increased the level of TNF in the serum, liver and spleen of lipopolysaccharide (LPS)-treated animals. In tissue cultures RU 38486 induced the TNF synthesis of myeloid cells and increased the TNF production of genetically modified HeLa cells, which synthesize TNF constitutively. Normal and tumor cell cultures exhibited increased sensitivity toward TNF in the presence of mifepristone.
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PMID:Effect of RU 38486 on TNF production and toxicity. 149 22

Phytohemagglutinin (PHA) injection induces transient protease-sensitive traffic of lymphocytes in skin and other tissues in several species. Examination of the possible roles of cytokines in such reactions showed that recombinant bovine and human tumor necrosis factor (TNF)-alpha potently induce dose-dependent lymphocyte traffic in pig skin (and in other tissues including the draining lymph nodes) with early kinetics and a morphology of the inflammatory reaction similar to that of PHA (peaking 9-12 h). Recombinant human interleukin (IL)-1 alpha also induces dose-dependent lymphocyte traffic, but it peaks at 4 h. Entry of labeled lymphocytes into inflammatory sites induced by PHA, TNF-alpha and IL-1 alpha, but not into normal skin, is inhibited by approximately 80% by their pretreatment with trypsin, indicative of the induction of endothelial determinants recognized by protease-sensitive surface molecules on the lymphocytes. Even the minimal lymphocyte traffic induced by interferon-gamma and lipopolysaccharide was similarly protease sensitive. At the earliest stage (approximately 2 h) of significant induction of lymphocyte entry by TNF-alpha and IL-1 alpha the inductive signal for each appears easily saturated. Thus lymphocyte entry is little increased by increasing low cytokine doses over 100-fold: However, these reactions are additive, and this was used to confirm that they are distinct from each other and from PHA. A further distinction was revealed by the homing of lymphocytes pretreated with pertussis toxin: such lymphocytes were greater than 90% inhibited in their homing to tissues through constitutive high endothelial venules (HEV) and greater than 60% inhibited in homing to TNF-alpha and IL-1 alpha skin sites, but unaffected in homing to PHA skin sites (like most non-HEV-mediated traffic). Moreover, potent chicken anti-TNF-alpha, which prevented TNF-induced lymphocyte entry, did not affect PHA-induced traffic. Thus, these three agents which induce peripheral lymphocyte traffic appear to involve different mechanisms as shown by differences in (i) their kinetics; (ii) the effect of anti-TNF-alpha and (iii) the effect of pertussis toxin treatment of the lymphocytes and by the fact that their inductive mechanisms are additive in effect.
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PMID:Active lymphocyte traffic induced in the periphery by cytokines and phytohemagglutinin: three different mechanisms? 151 13

Previous findings have shown that lipopolysaccharide (LPS)-activated human monocytes express cytokines (CKs) on their membrane. Furthermore, those associated to membrane products such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 have been demonstrated to exert many biological activities. In this paper, evidence is provided that human polymorphonuclear cells (PMN) exhibited an increased phagocytic capacity following incubation with either lipid A (LA)-activated autologous monocytes or supernatants recovered from LA-stimulated mononuclear cell cultures. In order to investigate the possible role of monocyte membrane-associated TNF-alpha, IL-1 alpha and IL-1 beta in the modulation of PMN activity, in a separate series of experiments LA-activated monocytes or LA-activated supernatants were pretreated with anti-recombinant human (Rhu) TNF alpha, anti-Rhu IL-1 alpha and anti-Rhu IL-1 beta monoclonal antibodies (MoAbs), respectively. Such an approach gave rise to an abrogation of monocyte-mediated triggering effect on PMN functional capacity. Taken together, these data suggest that activated monocytes can upregulate PMN phagocytosis by a cell-to-cell contact mechanism, likely related to membrane-associated CKs.
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PMID:Enhancement of polymorphonuclear cell phagocytosis by lipid A-activated monocytes via cell-to-cell contact. A possible role for membrane-associated cytokines. 151 25

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

As a corollary to their anatomic location, alveolar macrophages (AM) have a lower threshold for generating some physiologic functions than peritoneal macrophages (PM). In this study, we examined both of these populations for their ability to bind the lectin Griffonia simplicifolia-IB4 (GSIB4) and to produce tumor necrosis factor (TNF)-alpha. The results showed that these two responses were concurrently expressed in activated macrophages, although they differed in magnitude when AM and PM were compared. Following in vitro incubation, AM from lipopolysaccharide-treated rats demonstrated a higher percentage of GSIB4 positivity and TNF production when compared with their respective PM. Since prostaglandin E2 can regulate the expression of some macrophage activities, experiments were conducted to determine whether this could also affect the ability of macrophages to bind the GSIB4 lectin. Neither the administration of indomethacin nor exogenous prostaglandin E2 altered the expression of this marker. Conversely, these treatments produced significant changes in TNF-alpha production in both alveolar and peritoneal macrophages. When the concurrent expression of GSIB4 lectin binding and TNF-alpha production was analyzed, AM from lipopolysaccharide-treated rats demonstrated both superior GSIB4 positivity and TNF-alpha production compared with all other macrophages examined. The results of this work show that AM and PM differ in their expression of GSIB4 binding and TNF-alpha production. These differential responses may be important in determining the level of activity of macrophages that are participating in an immune response.
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PMID:The concurrent expression of Griffonia simplicifolia-IB4 binding and tumor necrosis factor-alpha differs between alveolar and peritoneal macrophages. 153 38

Differentiation factor (D factor), also called leukemia inhibitory factor (LIF), is a glycoprotein that has been increasingly recognized to possess a wide range of physiological activities. We examined the possibility that the administration of D factor may confer beneficial effects and enhance host resistance against lethal endotoxemia. A single intravenous dose of recombinant human D factor completely protected C57/Bl6 mice from the lethal effect of Escherichia coli endotoxin (lipopolysaccharide [LPS]). The protective effects were dose dependent and observed when administered 2-24 h before LPS. Previous work has shown that interleukin 1 (IL-1) and tumor necrosis factor (TNF) also protect against a subsequent LPS challenge in a dose-dependent manner. When human D factor was combined with sub-protective doses of IL-1 beta or TNF-alpha, there was dramatic synergistic protection against a subsequent lethal LPS challenge.
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PMID:Differentiation factor/leukemia inhibitory factor protection against lethal endotoxemia in mice: synergistic effect with interleukin 1 and tumor necrosis factor. 155 84


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