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 combined effect of hydrocortisone (HC) and interferon-gamma and -alpha (IFN-gamma and -alpha) on human blood monocytes (Mo) interleukin 1 (IL 1) secretion was investigated. IL 1 was generated by treating the fresh or aged Mo with lipopolysaccharide (LPS), and quantitated by radioimmunoassay (RIA). Hydrocortisone, at the pharmacological attainable concentration of 10(-5) molar (M), markedly suppressed fresh Mo IL 1 secretion but had no effect at lower tested doses. Addition of IFN-gamma enhanced the IL 1 secretion of fresh Mo; however, the simultaneous addition of 10(-5) M HC and IFN-gamma resulted in marked suppression of the monokine release. Monocytes, when cultured in vitro for three days, lost the capacity to secrete IL 1. The loss of IL 1 secretory potential of aged Mo was prevented by preincubating them with IFN-gamma prior to LPS stimulation. IFN-alpha was ineffective in this regard. Aged Mo, pretreated with the combination of IFN-gamma and HC were still able to secrete abundant quantities of IL 1, demonstrating the failure of HC to suppress the IFN-gamma-induced augmentation of IL 1 secretory potential. Even suprapharmacologic doses of HC (10(-4) M) did not inhibit this enhancement and actually further augmented it. Thus, therapeutic concentrations of HC suppress IL 1 secretion of fresh Mo even in the presence of IFN-gamma; however, therapeutic or suprapharmacologic concentrations of HC do not inhibit the IL 1 secretory capacity of IFN-gamma-treated aged Mo.
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PMID:Failure of hydrocortisone to suppress the interferon-gamma-induced augmentation of interleukin 1 secretion of aged human monocytes. 313 48

There is a marked decrease in the viability, in vitro, of dense, immature rat thymocytes over a 4 h incubation period. The addition of a monokine of relative molecular weight 36,000 derived from cultured rat peritoneal macrophages which had been previously stimulated with lipopolysaccharide prevented these cells from dying. The early release of this factor, together with preliminary results of its physical and functional properties suggest that it is distinct from the well characterized monokines. The macrophage factor was found to bind in competition with a monoclonal antibody directed against a common determinant on the Ia antigen complex, but also to bind non-competitively with a monoclonal antibody to a strain-specific epitope on Ia. Based on the results of experiments using a fractionated thymic cell model, it would appear that this monokine binds to the Ia protein complex on the cell surface of thymic epithelial cells, causing them in turn to release an activity which is responsible for the survival of thymocytes.
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PMID:A monokine which binds to class II histocompatibility proteins. 315 22

The addition of picogram quantities of bacterial products to rat thymic cells in culture produced a doubling of the proliferative response to suboptimal levels of Concanavalin-A (Con-A). This effect was prevented by the depletion of adherent cells which comprised less than 0.1% of the total population. The response was restored by the addition of supernatants from peritoneal macrophages which had been stimulated 2 h previously with lipopolysaccharide. Treatment of these supernatants with phenylglyoxal, an inhibitor of interleukin-1 (IL-1), did not prevent the stimulatory effect. Augmentation of the thymocyte proliferative response could also be achieved by the addition of a partially purified monokine of relative molecular weight (Mr) 36,000 which is biochemically and functionally distinct from IL-1 and by a monoclonal antibody which binds to a common determinant on the Ia molecule. Fractionation of the thymic cells on a density gradient yielded a buoyant population which accounted for the majority of the proliferative activity and a dense fraction which was poorly responsive to the mitogen. The addition of the monokine to this latter fraction produced a significant increase in proliferation in response to Con-A. It is proposed that in the thymus, bacterial products stimulate thymic macrophages to release the Mr 36,000 monokine which in turn stimulates the thymic epithelial cells to release products which promote the survival and maturation of immature thymocytes. This work has implications for the regulation of thymocyte maturation.
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PMID:Augmentation of mitogen-induced thymocyte proliferation by bacterial products is mediated by an Mr 36,000 monokine. 315 23

Using a highly specific rabbit antisera directed against murine tumor necrosis factor (TNF), immunohistochemical localization of this monokine was performed in cultured mouse peritoneal macrophages. Resident macrophages did not express TNF even after stimulus with lipopolysaccharide (LPS). In contrast, 12% of macrophages elicited with Freund's adjuvant stained positively and up to 60% were positive after LPS stimulation. Analysis of the kinetics of expression revealed that maximal staining occurred from 1-3 hours after stimulus with disappearance of staining by 12 hours. Both a membrane and cytoplasmic pattern of staining could be demonstrated. The presence of plasma membrane TNF was confirmed by scanning electron microscopy. Northern blot analysis and bioassay revealed that the kinetics of TNF mRNA synthesis corresponded to the appearance of the protein while its disappearance corresponded to the appearance of TNF in the supernate. Thus, TNF synthesis and secretion could be histochemically demonstrated. These findings support the notion that TNF production is a characteristic of activated macrophages and that such cells display membrane-associated TNF at least transiently after stimulation.
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PMID:Immunohistochemical demonstration of cytoplasmic and membrane-associated tumor necrosis factor in murine macrophages. 320 18

The secretions of interleukin 1 (IL-1), tumour necrosis factor alpha (TNF), and prostaglandin E2 (PGE2) of low-dose E. coli lipopolysaccharide (LPS)-stimulated human monocytes (M phi) were investigated in an endotoxin (ET)-free milieu (less than 1.6 pg LPS/ml). Human M phi cultures from nine healthy men were stimulated with 0, 12.5-500, and 250,000 pg LPS/ml as measured by a very sensitive Limulus test. The IL-1 activity was tested by the mouse costimulatory thymocyte (LAF) assay, which was thoroughly standardized and characterized (interassay variation 22-24%, intra-assay variation 3-7%). Spontaneous M phi secretions of IL-1, TNF, and PGE2 were negligible, but 12.5 pg LPS/ml significantly stimulated the secretions of these M phi products and the monokine responses to 500 and 250,000 pg LPS/ml were almost in the same range. It was demonstrated that the secretions of IL-1-TNF and TNF-PGE2 were strongly correlated. Pronounced interindividual differences in LPS responsiveness were demonstrated, and two low-responders, one of whom was HLA-DR1,2-positive, were identified. Three first-degree relatives of the DR1,2-positive low-responder had similar low responses. Furthermore, M phi cultures were prepared weekly for 4 weeks from four HLA-DR different men and the only DR2,2 homozygous individual had low monokine responses. In conclusion, stable interindividual differences in in vitro monokine and PGE2 secretions of LPS-stimulated M phi were demonstrated. It is suggested that HLA-DR2-positive individuals may be low responders.
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PMID:Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences. 326 Jun 83

We studied the effect of toxic-shock-syndrome toxin-1 (TSST-1) on production of tumor necrosis factor (TNF) by human monocytes. Adherent mononuclear cells were stimulated with TSST-1 and their supernatants assayed for TNF by using L929 cells in a cytotoxicity assay. TSST-1 stimulated production of TNF over a wide range of concentrations. The cytotoxicity of monocyte supernatants was neutralized by antibody to TNF but not by antibody to interleukin-1 or by normal rabbit serum. TSST-1 and lipopolysaccharide (LPS) had a synergistic effect on monokine production. Monocytes "primed" with TSST-1 produced more interleukin-1 and TNF in response to LPS than did unprimed cells. Treating monocytes with LPS before TSST-1 and co-incubating the two agents with cells for 24 h also enhanced monokine production under some circumstances. These studies suggest a role for TNF in the pathogenesis of toxic shock syndrome, as a consequence of induction by TSST-1 alone or the synergistic effects of several bacterial products.
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PMID:Production of tumor necrosis factor by human monocytes in response to toxic-shock-syndrome toxin-1. 326 47

Endotoxin depresses cytochrome P450 levels when injected into animals. The purpose of this study was to determine whether endotoxin itself, or monokine(s) released in response to endotoxin administration are responsible for this effect. Cytochrome P450 levels and drug metabolizing activities were measured in endotoxin resistant C3H/HeJ mice 24h after single intraperitoneal injections of either lipopolysaccharide (LPS), a semipurified murine monokine preparation containing interleukin-1 (IL-1), or murine recombinant IL-1. In endotoxin sensitive C3H/HeN mice, LPS (0.5 mg/Kg) decreased total cytochrome P450 levels, benzphetamine demethylase activities, and ethoxyresorufin-0-deethylase activities. This dose of LPS did not alter cytochrome P450 levels or activities in the C3H/HeJ mice. However, after injection of the semipurified monokine preparation or the recombinant IL-1, there were significant decreases in cytochrome P450 levels and activities similar to the decreases observed with LPS in the C3H/HeN mice. These findings suggest that the alterations in hepatic cytochrome P450 seen with endotoxin injection are mediated, at least in part, by IL-1.
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PMID:Interleukin-1 (IL-1) depresses cytochrome P450 levels and activities in mice. 329 45

Tumour necrosis factor (TNF) or cachectin is an important mediator of endotoxic activity. To investigate the production of TNF from human mononuclear cells (MNC) in response to lipopolysaccharide (LPS), we developed a sensitive and specific enzyme immunoassay (ELISA) and a cytotoxicity bioassay for TNF. The ELISA utilizes the biotin/avidin system and includes four incubation steps. The detection limit was 25 pg recombinant TNF (rTNF)/100 microliter. There was no interference of medium, serum, plasma, spinal fluid, or urine and no cross-reaction with natural or recombinant IL-1-alpha, IL-1-beta, IL-2, IFN-gamma, or lymphotoxin (TNF-beta). Recovery of TNF added to the media was 85-123% (n = 22). The relative standard deviations within and between assays were 7% and 8%, respectively. TNF-induced cytotoxicity was measured on actinomycin-D-treated L-M mouse fibroblasts. The detection limit in this bioassay was 0.5 U/30 microliter or 12.5 pg/30 microliter of rTNF. IL-1-alpha and IL-1-beta slightly inhibited the cytotoxic activity of rTNF. In this bioassay, cytotoxic activity (50-300 U/ml) was detected only when MNC were stimulated with high concentrations of LPS (100-1000 ng/ml). In contrast, using 0.01-100 ng/ml of LPS, the ELISA detected TNF in a dose-dependent manner (0.25 ng/ml to 40 ng/ml). It is concluded that TNF is liberated from human blood MNC if stimulated with minute amounts of LPS. It is suggested that human TNF may be secreted in a relatively inactive form or that inhibitors of TNF are generated along with the monokine. Because of this, and because commonly used bioassays for TNF fail to distinguish between TNF and lymphotoxin, specific ELISA are recommended to supplement TNF bioassays.
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PMID:Detection of tumour necrosis factor from lipopolysaccharide-stimulated human mononuclear cells by enzyme-linked immunosorbent assay and cytotoxicity bioassay. 334 Aug 24

Mo3e is a protease-sensitive membrane antigen (p75,50) selectively expressed by human monocytic cells (monocytes and U-937 cells) stimulated in vitro by exposure to a variety of activating factors, including phorbol diester compounds, bacterial lipopolysaccharide (LPS), and muramyl dipeptide (MDP)(R.F. Todd et al., J. Immunol. 135, 3869, 1985). Here we report that primary and multiply-passaged cultures of HUVEC also express the Mo3e determinant after stimulation by phorbol myristate acetate (PMA) and related inducers of protein kinase C. As measured in a radioimmunoassay of anti-Mo3e antibody binding to monolayer cultures of HUVEC, unstimulated cells bore little if any Mo3e. After culture for 4-120 hr in medium containing PMA, 4 beta-phorbol dibutyrate, 4 beta-phorbol didecanoate, or mezerein (each at a concentration of 81 nM), or 1-oleoyl-2-acetoyl-sn-3-glycerol (1 mM), HUVEC were found to selectively express the Mo3e determinant. The magnitude of expression was dependent upon the concentration of the stimulus, maximal by 24 hr, and inhibited by cycloheximide. The combination of PMA and the calcium ionophore, ionomycin, had an additive or synergistic effect on HUVEC Mo3e expression. The biologically inactive phorbol compounds 4 beta-phorbol and 4 alpha-phorbol didecanoate failed to stimulate Mo3e expression. Also inactive as inducers of HUVEC Mo3e expression were crude lymphokine and monokine supernatants, recombinant human lymphokines (interferon-gamma and interleukin-2), recombinant human monokines (interleukin-1 and tumor necrosis factor), bacterial cell wall products including LPS and MDP, pharmacologic agents that increase intracellular cyclic adenosine monophosphate (prostaglandin E2, cholera toxin, theophylline, isoproterenol and isobutylmethylxanthine), lectins (Con A and PHA), and heparin. These results indicate that Mo3e is an inducible plasma membrane antigen of not only mononuclear phagocytes but also cultured HUVEC.
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PMID:Expression of Mo3e antigen by cultured human umbilical vein endothelial cells (HUVEC) stimulated by phorbol myristate acetate (PMA) and related pharmacological inducers of protein kinase C. 334 69

Interleukin 1 (IL 1) is a principal mediator of the host immune response to microbial challenge. Accessory cells of the monocyte-macrophage series are a major source of this cytokine and are also chronically parasitized by protozoa of the genus Leishmania. This suggests that characterization of the macrophage IL 1 response to Leishmania would increase our understanding of the regulation of host immunity to these organisms. In the present study, the macrophage IL 1 response to Leishmania donovani was examined because infections with this organism have findings consistent with parasite-specific T cell unresponsiveness. Cytokine activity was measured either by direct stimulation or by co-stimulation of thymocytes. Conditioned media from BALB/c resident peritoneal macrophages infected with amastigotes of L. donovani contained no more IL 1 than did supernatant fluids of control cells. In contrast, supernatants from cells stimulated with lipopolysaccharide or heat-killed Listeria monocytogenes had significantly increased cytokine content. Resident cells infected with L. donovani for 4 hr before being stimulated with Listeria demonstrated a suppressed IL 1 response (approximately 40% of Listeria alone) to this secondary particulate stimulus. In contrast, the secondary response of leishmania-preinfected cells to lipopolysaccharide was not affected. To examine whether accessory cell nonresponsiveness to L. donovani (with respect to IL 1) was related to the state of macrophage activation, elicited peritoneal macrophages obtained by injection of proteose peptone were also studied. These cells responded to stimulation with lipopolysaccharide and fixed Staphylococcus aureus with increases in intracellular, membrane, and secreted cytokine activities. In contrast, L. donovani failed to induce any of these activities. This was found to be the case irrespective of whether amastigotes were alive or killed or opsonized with specific antibodies. Elicited cells preinfected with Leishmania responded normally to secondary stimulation with lipopolysaccharide, but not S. aureus (64% of Staphylococcus alone). In addition, attachment and penetration of L. donovani promastigotes and their subsequent conversion to amastigotes within macrophages failed to induce IL 1 synthesis. The findings of this study indicate that L. donovani has the ability to both evade and suppress the macrophage IL 1 response. Because this monokine provides an obligatory signal during macrophage-dependent T cell activation, evasion of signal transduction for IL 1 synthesis may be related to defects in cell-mediated immunity which occur during infections with this organism.
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PMID:Parasite accessory cell interactions in murine leishmaniasis. I. Evasion and stimulus-dependent suppression of the macrophage interleukin 1 response by Leishmania donovani. 349 91


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