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)

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

Evidence is presented that upon stimulation with endotoxin (lipopolysaccharide, LPS), Kupffer cells, the body's largest pool of sessile macrophages, synthesize and liberate a factor whose immunological, cytotoxic and chemical properties are those described for tumor necrosis factor (TNF)-alpha. Hepatocytes and sinusoidal endothelial cells do not produce detectable amounts of this protein. Ten nanograms of LPS per ml medium are sufficient to stimulate a substantial release of this mediator. Recombinant interferon-gamma (rIFN gamma) per se is a poor inducer of TNF release. Costimulation with endotoxin and rIFN gamma shows only a slight increment in the release of this cytotoxic factor, relative to LPS alone. Exposure of Kupffer cells to the Ca2+ ionophore A23187 or to elicitors of the oxidative burst and superoxide production, e.g. zymosan or phorbol 12-myristate 13-acetate, stimulates only a fraction (20%) of the TNF release seen after endotoxin challenge. Prostaglandin E2, the synthesis of which is strongly enhanced after challenge of rat Kupffer cells with LPS, suppresses the release of TNF by these cells. This autoregulatory mechanism may explain the kinetics of TNF production by stimulated Kupffer cells. Dexamethasone is another important mediator capable of reducing the LPS-elicited TNF formation. An effect of the glucocorticoid hormone can still be provoked if it is added simultaneously with or shortly after LPS. This rapid action requires a mechanism that is different from the time-consuming one leading to the inhibition of prostaglandin synthesis in Kupffer cells.
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PMID:The release of tumor necrosis factor from endotoxin-stimulated rat Kupffer cells is regulated by prostaglandin E2 and dexamethasone. 314 53

Dexamethasone is known to have an inhibitory effect on IL-1 production. To determine the mechanism(s) of this inhibition, adherent human blood monocytes were stimulated with Escherichia coli lipopolysaccharide (LPS) (10 micrograms/ml) in the presence of dexamethasone. Nuclear transcription run-off assays showed that LPS induced IL-1 beta gene transcription two- to fourfold and that this induction was unaffected by dexamethasone exposure (10(-5) M). The lack of dexamethasone's transcriptional effects was further supported by the absence of any significant change in IL-1 beta mRNA accumulation between LPS-stimulated monocytes exposed or unexposed to dexamethasone, as determined by Northern blot analysis. Posttranscriptionally, dexamethasone was found to have multiple effects: slight prolongation of IL-1 beta mRNA half-life, moderate inhibition of translation of the IL-1 beta precursor, and profound inhibition of the release of IL-1 beta into the extracellular fluid. The data indicate that IL-1 beta is first translated as the 33,000-D pro-IL-1 beta protein, the predominant intracellular form, and the processed to a 17,500-D IL-1 beta protein before or during extracellular transport. The major inhibitory effects of dexamethasone appear to be directed at the translational and posttranslational steps involved in these events.
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PMID:Dexamethasone inhibition of interleukin 1 beta production by human monocytes. Posttranscriptional mechanisms. 325 19

Three secretory products of the macrophage, interleukin 1 (IL-1), tumor necrosis factor/cachectin (TNF) and hepatocyte stimulating factor/interleukin 6 (IL-6) modulate liver protein synthesis during the acute phase response. Induction of serum amyloid A (SAA) synthesis is one of the most notable acute phase changes in liver proteins, with maximal SAA concentrations varying over a thousand-fold range in proportion to the amount of tissue injury and cell necrosis. Exogenous IL-1 and TNF induce SAA synthesis in vivo and in vitro, while exogenous IL-6 is a far less potent stimulus of in vivo SAA gene expression. Dexamethasone (DEX), a potent inhibitor of macrophage IL-1, TNF and IL-6 synthesis, was utilized to analyze the endogenous mediators of SAA synthesis in mice injected with lipopolysaccharide (LPS). DEX, although itself exhibiting the capacity to stimulate SAA synthesis to a limited extent, significantly reduced LPS induced SAA production. However, DEX did not reduce, but rather potentiated, IL-1 and TNF stimulated SAA production, indicating that these monokines do not require macrophage products to mediate their in vivo SAA inducer activity. SAA synthesis was observed in adrenalectomized mice, following administration of LPS, IL-1 and TNF, indicating that SAA induction by monokines is not secondary to corticosteroid release.
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PMID:Dexamethasone modulation of LPS, IL-1, and TNF stimulated serum amyloid A synthesis in mice. 326 78

The J111 histiocytic cell line is capable of producing human alpha 1-antichymotrypsin (alpha 1 ACh) in culture. The protein is secreted rather than stored in the cell, has a similar size to plasma alpha 1 ACh (68 kDa) and can complex with human cathepsin G. Dexamethasone and culture supernatants from U937 monocyte-like cells and alveolar macrophages, but not bacterial lipopolysaccharide, stimulate alpha 1ACh secretion by J111 cells. The J111 cell line thus provides a useful tool for the study of factors controlling alpha 1ACh synthesis in vivo.
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PMID:Production of alpha 1-antichymotrypsin by the J111 cell line. 326 5

We have investigated the modulating effect of steroids on the in vitro production of tumour necrosis factor (TNF) by lipopolysaccharide (LPS)-stimulated human monocytes. Dexamethasone, at concentrations ranging from 10(-8) to 10(-6) M, and cortisol, at concentrations 10(-7) and 10(-6) M, suppressed the TNF production in a dose-dependent manner. The highest concentrations of dexamethasone or cortisol reduced the TNF production to 21 +/- 2% and 48 +/- 8% of the control value, respectively. The effect of dexamethasone was time dependent, and an incubation time of 48 hr was required to reduce the TNF production to 21% of control. The effect of dexamethasone decreased when the incubation time became shorter, and the mean TNF production ranged from 49% to 72% of control when dexamethasone was added later than 8 hr before LPS addition, at the time of LPS addition, or within 1 hr after LPS addition. The magnitude of the TNF-suppressing effect of dexamethasone varied greatly from donor to donor. Only the glucocorticoids, and not the sex steroids or the mineralocorticoids, significantly reduced the TNF production.
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PMID:Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. 335 May 75

The effect of intravenously injected dexamethasone on the febrile response of rabbits to Polyinosinic: Polycytidylic acid (Poly I:C), lipopolysaccharide (LPS) and interleukin 1/endogenous pyrogen (IL1/E.P.) was studied. Dexamethasone (1 mg/kg) attenuated the febrile response to Poly I:C (5 micrograms/kg) but only if administered between 0.5 to 2 h before Poly I:C. If it was given after Poly I:C this resulted in a potentiation of the fever. Antagonism of the febrile response to Poly I:C by dexamethasone pre-treatment was dose-dependent and a maximal effect was observed with 3 mg/kg, a higher dose (6 mg/kg) resulted in a lesser effect on the Poly I:C fever. DEX injected alone (0.5-6 mg/kg) did not have any effect on body temperature. Fevers in response to LPS (50 ng/kg) and IL1/E.P. were also attenuated by dexamethasone. It is concluded that Poly I:C, LPS and IL1/E.P. induce fever by a common mechanism which is either directly or indirectly inhibited by dexamethasone.
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PMID:Dexamethasone pre-treatment is antipyretic toward polyinosinic: polycytidylic acid, lipopolysaccharide and interleukin 1/endogenous pyrogen. 349 38

Angiotensin converting enzyme (ACE;EC 3.4.15.1), or kininase II, was studied in serum, cultured endothelial cells from cord artery, in macrophages of humans, and in serum and purified plasma membranes of rats following treatment with inducers of ACE biosynthesis. ACE activity was measured in biological fluids with an enzyme kinetic method employing synthetic 1-hipp-1-his-l-leu tripeptide as a substrate, and with a new method using 125I-labelled specific inhibitor of ACE as a sensitive probe for ACE binding sites. The latter technique also proved suitable for the quantification of ACE in cells. Anti-human ACE antibody was employed for immunofluorescence studies in human cells. Dexamethasone treatment caused an increase in ACE in cultured human endothelial cells, macrophages and in rat pulmonary plasma membranes, but failed to increase serum ACE activity in rats. Captopril and enalapril treatment of hypertensive patients increased total serum ACE, the increase being evident after removal of the active drug from the serum by prolonged storage or chloramine T treatment (captopril) or by dialysis (enalapril). Captopril increased the ACE content of endothelial cells and macrophages. Macrophages appeared sensitive to captopril induction of ACE biosynthesis after pre-stimulation with Escherichia coli lipopolysaccharide. Dexamethasone treatment potentiated the known induction of ACE in rat pulmonary tissue. Thus ACE biosynthesis may be enhanced by three categories of treatment: (1) glucocorticoid; (2) macrophage activation; (3) ACE inhibitors. The precise mechanism of ACE induction and its possible biological relevance await further clarification.
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PMID:Regulation of angiotensin converting enzyme. 610 Jun 6

The inhibitors of angiotensin converting enzyme (ACE), captopril and enalapril, were found to increase ACE concentration in cultured human endothelial cells from cord artery as measured with a novel ACE assay employing MK 351A, an inhibitor of ACE, and with immunofluorescense labeling using anti-human lung ACE antibody. Dexamethasone (10 nM) also increased ACE and potentiated the increase of cellular ACE caused by captopril. Similar effects of ACE inhibitors were seen in cultured human macrophages, particularly after prestimulation with E. coli lipopolysaccharide. In Wistar Kyoto rats, captopril caused a 3-fold increase of serum ACE, while dexamethasone (40 ug/day, 14 days) did not increase serum ACE. Combined treatment with captopril and dexamethasone caused a 5-fold increase of ACE in purified lung plasma membranes. ACE inhibitors induce increased ACE biosynthesis in endothelial cells, and in macrophages. The rise of cellular ACE with ACE inhibitors is potentiated by glucocorticoid.
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PMID:The induction of angiotensin converting enzyme by its inhibitors. 631 71

One of the major inducible cytokines secreted by mononuclear phagocytes is macrophage inflammatory protein 1 (MIP-1), which consists of two homologous polypeptides, MIP-1 alpha and MIP-1 beta. MIP-1 alpha possesses chemotactic and stimulatory activities for lymphocytes, eosinophils, and monocytes and may play a role in various pulmonary inflammatory conditions. We investigated the expression and release of MIP-1 alpha from human peripheral blood monocytes (PBM) and alveolar macrophages (AM) after stimulation with lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha, and interferon-gamma and the inhibitory effects of corticosteroids. LPS and IL-1 beta only enhanced MIP-1 alpha mRNA and protein in a dose- and time-dependent fashion. Dexamethasone (10(-9) to 10(-4) M) inhibited the basal and induced production and expression of MIP-1 alpha. In PBM, dexamethasone (10(-6) M) reduced LPS- and IL-1 beta-stimulated production of MIP-1 alpha protein by 50 and 63%, respectively, maximally at 24 h, whereas the inhibition of mRNA expression occurred maximally at 4 h. Similar trends were observed for AM. MIP-1 alpha mRNA decay was only slightly decreased in the presence of dexamethasone. Inhibition of LPS-induced MIP-1 alpha mRNA by dexamethasone was attenuated by the protein synthesis inhibitor cycloheximide, indicating the involvement of a protein intermediate. Corticosteroids are a potent inhibitor of IL-1 beta- and LPS-induced expression of MIP-1 alpha through mechanisms involving mainly inhibition of transcription and to a minor degree by reducing mRNA stability. Corticosteroids may be effective anti-inflammatory agents by preventing the expression of chemokines such as MIP-1 alpha.
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PMID:Corticosteroid inhibition of macrophage inflammatory protein-1 alpha in human monocytes and alveolar macrophages. 748 16


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