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)

Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases. In vitro, neopterin is released into the supernatant by peripheral blood-derived monocytes/macrophages upon stimulation with gamma-interferon. In parallel, cleavage of tryptophan by indoleamine 2,3-dioxygenase is induced. We report here that the human myelomonocytic cell line THP-1 forms neopterin and degrades tryptophan upon treatment with gamma-interferon. Like in macrophages alpha-interferon and beta-interferon induce these pathways only to a much smaller degree. The action of interferons is enhanced by cotreatment with tumor necrosis factor alpha, lipopolysaccharide, or dexamethasone. gamma-Interferon-induced neopterin formation and indoleamine 2,3-dioxygenase activity are increased by raising extracellular tryptophan concentrations. The pattern of intracellularly formed pteridines upon stimulation with gamma-interferon shows the unique characteristics of human monocytes/macrophages. Neopterin, monapterin, and biopterin are produced in a 50:2:1 ratio. Thus, the THP-1 cell line provides a permanent, easily accessible in vitro system for studying the induction and mechanism of neopterin formation.
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PMID:Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment. 211 May

Tryptophan degradation in mice initiated by indoleamine 2,3-dioxygenase was characterized, taking advantage of its induction by bacterial lipopolysaccharide. Our results demonstrated that in various tissues, N-formylkynurenine produced by the dioxygenase from tryptophan was rapidly hydrolyzed into kynurenine by a kynurenine formamidase, but it was not further metabolized. The localization in the liver and kidney of the kynurenine-metabolizing enzymes suggested that kynurenine thus formed was transported by the bloodstream to those two organs to be metabolized. In fact, the plasma kynurenine level increased in parallel with the induction of the dioxygenase by lipopolysaccharide, and kinetic analysis indicated that at the maximal induction of the enzyme there was a 3-fold increase in the kynurenine production. The major metabolic route of kynurenine was excretion in urine as xanthurenic acid. This increase in the kynurenine production was not explained by L-tryptophan 2,3-dioxygenase in the liver, because during the induction of indoleamine 2,3-dioxygenase, the hepatic enzyme level was substantially suppressed. These findings indicated that indoleamine 2,3-dioxygenase actively oxidized tryptophan in mice and that its induction resulted in an increase in tryptophan degradation.
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PMID:Tryptophan degradation in mice initiated by indoleamine 2,3-dioxygenase. 241 35

Interferon (IFN)-induced tryptophan degradation, catalyzed by indoleamine 2,3-dioxygenase (IDO), has been shown to mediate antimicrobial activity in epithelial cells. IDO activity has also been augmented in peripheral blood mononuclear cells (PBMC) treated with IFN or interleukin-2 (IL-2). The effector cells in this population have now been further characterized. PBMCs were isolated from normal donors, separated into monocyte and lymphocyte populations by plastic adherence, treated with IFN or IL-2, and cultivated in medium supplemented with [3H]tryptophan. Culture supernatants were collected after a 48-h incubation and fractionated by high-performance liquid chromatography; radioactivity was determined in fractions corresponding to tryptophan and its metabolites. IFN-gamma and IFN-beta induced IDO activity only in monocytes (plastic-adherent, nonspecific esterase-positive PBMCs). The induction of IDO activity by IL-2 required both monocytes and lymphocytes. Interaction was required between these populations for induction of IDO by IL-2, due to production of IFN-gamma by T lymphocytes, with subsequent IFN-gamma-mediated induction of IDO in monocytes. A number of myeloid cell lines as well as monocyte-derived macrophages were also tested for their ability to be induced to degrade tryptophan in response to IFN treatment. Monocyte-derived macrophages were found to retain their capacity to be induced by IFN-gamma and IFN-beta to degrade tryptophan after differentiation, and to possess seven times more IDO activity per cell than IFN-induced monocytes. However, the presence of lipopolysaccharide (LPS) in the culture medium was required for the maximum induction of IDO activity by IFN-beta. Furthermore, higher concentrations of LPS were sufficient to induce IDO activity in macrophages in the absence of exogenous IFN.
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PMID:Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes. 246 22

The capacity of recombinant interferon-alpha, -beta and -gamma, of bacterial lipopolysaccharide and of recombinant tumour necrosis factor-alpha to induce indoleamine 2,3-dioxygenase and synthesis of pteridines was studied in human peripheral blood mononuclear cells, human macrophages and normal dermal fibroblasts. The action of interferon-alpha and -beta on macrophages was supported by lymphocyte factors as indicated by the effect of these mediators in the absence or presence of lymphocytes. Tumour necrosis factor-alpha alone was ineffective in peripheral blood mononuclear cells and macrophages, but it significantly increased the action of all three interferon species on macrophages and fibroblasts. Lipopolysaccharide directly affected macrophages or dermal fibroblasts and enhanced the effect of interferon-gamma. However, in the presence of lymphocytes, the action of lipopolysaccharide was mediated via interferon-gamma.
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PMID:Tumour necrosis factor-alpha and lipopolysaccharide enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells. 248 41

Interferon-gamma (IFN-gamma) previously has been shown to inhibit the replication of Chlamydia psittaci in epithelial cells by inducing indoleamine 2,3-dioxygenase, the enzyme that decyclizes tryptophan to N-formylkynurenine. The role of indoleamine 2,3-dioxygenase in IFN-mediated inhibition of C. psittaci in human macrophages has now been examined. Peripheral blood monocytes from normal donors were isolated and cultivated 10-14 days to allow differentiation to macrophages. Cells were then treated with either IFN-gamma or IFN-beta for 48 h before infection with sufficient C. psittaci to infect approximately 30% of the cells. Infected cells were incubated 24 h, at which time coverslips were fixed, stained with Giemsa, and examined for development of C. psittaci inclusions by light microscopy. Complete inhibition of inclusion development was observed with IFN-gamma. In the absence of lipopolysaccharide, inhibition of C. psittaci by IFN-beta was variable; however, in the presence of lipopolysaccharide, IFN-beta also completely inhibited C. psittaci replication. The addition of excess tryptophan to the culture medium at the time of infection partially reversed the effect of IFN on the inhibition of C. psittaci growth in a concentration-dependent manner. Indoleamine 2,3-dioxygenase activity was determined by measurement of the concentrations of tryptophan and its metabolites in the culture medium after reversed-phase high-performance liquid chromatography. Significant indoleamine 2,3-dioxygenase activity was observed only in macrophages treated with IFN-gamma or combined IFN-beta plus lipopolysaccharide, and resulted in greater than 50% of available tryptophan being catabolized in a 4-h period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-induced indoleamine 2,3-dioxygenase activity inhibits Chlamydia psittaci replication in human macrophages. 250 98

Gamma interferon (IFN-gamma) previously has been shown to block the replication of Toxoplasma gondii in fibroblasts by the induction of indoleamine 2,3-dioxygenase (IDO) activity. IFN-beta also is known to induce IDO activity in monocyte-derived macrophages, but its ability to block the growth of T. gondii has not been demonstrated. We found not only that the combination of IFN-beta and lipopolysaccharide induced greater IDO activity in monocyte-derived macrophages than did IFN-beta alone but that this combination also was effective in inhibiting the growth of T. gondii. In addition, the inhibition was reversed by the addition of exogenous tryptophan, thus demonstrating that a mechanism by which IFN-beta inhibited T. gondii replication was by the induction of IDO.
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PMID:Beta interferon inhibits Toxoplasma gondii growth in human monocyte-derived macrophages. 250 36

Since it is important the availability of a specific marker for interferon induction in vivo, we investigated the effect of different recombinant interferons and various cytokines on indoleamine 2,3-dioxygenase activity. Although with different magnitude, recombinant interferon-alpha A/D (Bgl II) hybrid, interferon-gamma and tumor necrosis factor, all increase the activity of this enzyme, whereas interleukin-1, recombinant interferon-alpha A and interferon-alpha D do not induce this activity in mice lung tissue. Dexamethasone is able to inhibit indoleamine 2,3-dioxygenase induction by lipopolysaccharide or by interferon-alpha A/D but it fails to prevent the induction by interferon-gamma.
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PMID:Induction of indoleamine dioxygenase by interferon in mice: a study with different recombinant interferons and various cytokines. 312 77

When C3H/He mice were treated with lipopolysaccharide, poly(I) X poly(C), or pokeweed mitogen, the serum interferon titer increased almost instantaneously (100-2000 units/ml), and then the pulmonary indoleamine 2,3-dioxygenase was induced 50- to 140-fold. The peaks corresponding to interferon induction always preceded (approximately 24 h) those corresponding to dioxygenase induction. In C3H/HeJ (lipopolysaccharide-nonresponder) mice, however, lipopolysaccharide was totally inert in induction of both interferon and dioxygenase, although treatment with poly(I) X poly(C) and pokeweed mitogen led to a remarkable increase in the serum interferon titer and the enzyme activity. When lymphocytes of C3H/HeJ mice were inactivated by X irradiation and then reconstituted by the transfer of spleen cells from C3H/He mice, both enzyme and interferon from C3H/HeJ mice thus treated were induced almost normally after the lipopolysaccharide treatment. In addition, murine interferon alpha/beta, which was injected intravenously in C3H/He or C3H/HeJ mice, almost instantaneously and dose-dependently induced the pulmonary enzyme, and at a dose of 10(5) units per mouse the enzyme activity was enhanced 20- to 26-fold in these two strains of mice. These results suggest that interferon, which is generated by the interaction of lymphocytes with lipopolysaccharide, poly(I) X poly(C), or pokeweed mitogen, is a mediator of indoleamine 2,3-dioxygenase induction in the mouse lung by these agents.
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PMID:Interferon: a mediator of indoleamine 2,3-dioxygenase induction by lipopolysaccharide, poly(I) X poly(C), and pokeweed mitogen in mouse lung. 348 42

The cellular localization of indoleamine 2,3-dioxygenase was studied in the mouse lung after induction by lipopolysaccharide treatment. No significant indoleamine 2,3-dioxygenase activity was detected in alveolar macrophages and type II epithelial cells, which were recovered by alveolar lavages and trypsin-treatment, respectively. To determine this enzyme activity in other types of lung cells, we prepared monodispersed lung cells (6.5 X 10(7) cells/lung) by incubation with 0.1% collagenase and 0.1% trypsin. In a Percoll isopycnic gradient, the dispersed cells were distributed with two peaks at the densities of 1.040 and 1.080 g/ml. The enzyme activity was recovered exclusively in the lighter fractions. As examined by electron microscopy or more quantitatively by using various marker enzyme activities, endothelial cells (angiotensin-converting enzyme as a marker enzyme of these cells), alveolar interstitial cells (prostaglandin dehydrogenase), type I epithelial cells, type II epithelial cells, alveolar macrophages (beta-glucuronidase), Clara cells (coumarin hydroxylase), and polymorphonuclear leucocytes (arylsulfatase) were distributed with peaks at the densities of 1.033, 1.040, 1.042, 1.045, 1.070, 1.082, and 1.093 g/ml, respectively. The distribution pattern of the indoleamine 2,3-dioxygenase activity exactly coincided with that of alveolar interstitial cells. The localization of this enzyme in alveolar interstitial cells was immunohistochemically confirmed with the anti-indoleamine 2,3-dioxygenase antibody.
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PMID:Induction of indoleamine 2,3-dioxygenase in alveolar interstitial cells of mouse lung by bacterial lipopolysaccharide. 634 79

The tryptophan decyclizing enzyme indoleamine 2,3-dioxygenase (IDO) was induced in human monocyte-derived macrophages (MDM) treated with human recombinant interferon-beta (IFN-beta) or interferon-gamma (IFN-gamma). Treated cells exhibited dose-dependent increases in IDO when assayed 48 hr after treatment. Cells exposed to IFN-gamma were observed to exhibit consistently higher peak levels of IDO when compared with cells incubated in the presence of IFN-beta. When IFN-beta-treated cells were incubated in the presence of specified amounts of bacterial lipopolysaccharide (LPS) or liposome-encapsulated muramyl tripeptide (MTP), peak IDO activity increased such that enzyme activity was comparable to maximal activity observed with IFN-gamma-treated cells. LPS and MTP also upregulated IFN-gamma-mediated IDO activity when suboptimal amounts of IFN-gamma were used. When macrophages were costimulated with various concentrations of human recombinant interleukin 1 alpha (IL-1 alpha), along with either maximum-stimulating amounts of IFN-beta or suboptimal amounts of IFN-gamma, IDO activity was upregulated in a manner similar to results obtained using the microbial products as stimuli. While neither IL-1 alpha or IL-1 beta was detected in culture supernatants from macrophages treated with either LPS or MTP (alone or in combination with IFN), IL-1 alpha was detected in cell lysates of macrophages treated with these upregulators. Although neutralizing antibody to IL-1 alpha abolished the upregulatory effect of exogenous IL-1 alpha, it had no effect on upregulation by LPS or MTP. This suggests that although LPS and MTP may induce production of cell-associated IL-1 alpha, upregulation of IDO activity by these agents is independent of IL-1 alpha production and may be mediated through distinct pathways.
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PMID:Upregulation of interferon-induced indoleamine 2,3-dioxygenase in human macrophage cultures by lipopolysaccharide, muramyl tripeptide, and interleukin-1. 772 88


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