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)

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.
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PMID:Regulation of rabbit acute phase protein biosynthesis by monokines. 246 85

Human blood monocytes isolated by centrifugal elutriation from healthy donors were tested for ability to produce membrane-associated antitumor monokine(s) in response to activation stimuli such as various types of interferon (IFN) and/or synthetic desmethyl muramyl dipeptide (norMDP). IFNs (alpha, beta, and gamma) and norMDP rendered blood monocytes cytotoxic to allogeneic A375 melanoma cells, as assayed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with any type of IFN for 16 h, and then fixed with paraformaldehyde, they did not show cytotoxicity to A375 cells, but when they were fixed after treatment with norMDP or lipopolysaccharide they showed significant cytotoxicity to A375 melanoma cells. This membrane-associated antitumor monokine induced by the synergistic actions of suboptimal concentrations of IFN-gamma and norMDP, was cytotoxic to HT-29 colon cancer cells as well as A375 melanoma cells, but not to actinomycin D-treated L-929 cells. The fixed monocyte-mediated cytotoxicity against A375 melanoma cells was completely inhibited by a specific anti-interleukin 1 alpha antiserum, but not by a specific anti-interleukin 1 beta antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated interleukin 1 alpha is involved through cell-to-cell contact in the host defense mechanism against cancer.
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PMID:Membrane-associated interleukin 1 alpha as a mediator of tumor cell killing by human blood monocytes fixed with paraformaldehyde. 246 72

Polymorphonuclear granulocytes (PMN) are potent producers of free oxygen-derived radicals. Since other granulocyte functions are affected by interleukins, we investigated whether free-radical production can be initiated by a similar mediator. For estimation of free radical production, SOD-inhibitable lucigenin-dependent chemiluminescence and SOD-inhibitable cytochrome C reduction were used. As a source of interleukins, serum-free 24 h culture supernatants of human mononuclear cells (MNC) stimulated with bacterial lipopolysaccharide were prepared. Addition of such supernatants to PMN caused stimulation of sod-inhibitable chemiluminescence and superoxide production. Studies with separated MNC showed that monocytes were the cellular source of the activity. Biochemically, this activity of the supernatants was due to a heat-labile glycoprotein with a MW of approx. 60 KDa. This mediator, termed granulocyte chemiluminescence inducer (GCI), appears to be distinct from interleukin 1 (alpha and beta) and interferon (alpha and gamma). In conclusion we describe a novel monokine, granulocyte chemiluminescence inducer (GCI), which initiates granulocyte free radical production. This interaction of monocytes and granulocytes may also in vivo constitute a new and potent pathway leading to stimulation of free oxygen production by granulocytes.
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PMID:A novel interleukin stimulating free radical production by granulocytes. 246 31

Bacterial endotoxin (lipopolysaccharide, LPS) has the property of inducing hyporesponsiveness or tolerance to its own effects. This phenomenon has been demonstrated in man and experimental animals. The cellular changes that contribute to LPS tolerance are not understood. One mechanism of tolerance could involve a diminished response to LPS by key effector cells such as macrophages. Here we describe experiments designed to determine the mechanism whereby LPS produces a hyporesponsive state to its own effects. Because of the importance of the monokine known as tumor necrosis factor-alpha (TNF-alpha) in mediating many of the diverse effects of LPS, we have studied induction of TNF-alpha at the mRNA and activity level in the murine macrophage-like cell line RAW 264.7. Hyporesponsiveness can be induced by exposure of RAW 264.7 cells to low doses of LPS for more than 6 h prior to challenge with a second, normally stimulatory dose of LPS. This hyporesponsiveness is characterized by a diminished ability of LPS to increase steady state levels of TNF-alpha mRNA, is not due to an increased rate of TNF-alpha mRNA degradation, and is specific for LPS since LPS-pretreated and control cells produce similar amounts of TNF-alpha in response to challenge with heat-killed Staphylococcal aureus. The presence of indomethacin during the primary and/or challenge LPS treatment has no effect on the induction of acquired hyporesponsiveness. Thus, cyclooxygenase products are probably not involved in the development of LPS-induced hyporesponsiveness. These studies provide the basis for a better understanding of the cellular mechanisms that contribute to LPS tolerance.
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PMID:Lipopolysaccharide induces hyporesponsiveness to its own action in RAW 264.7 cells. 248 Sep 60

The gold compounds, auranofin, sodium aurothiomalate, and triethyl gold phosphine have been demonstrated to inhibit various effector functions associated with monocyte-macrophage populations. Incubation of human peripheral blood monocytes and murine peritoneal macrophages with auranofin or triethyl gold phosphine inhibited TNF production in lipopolysaccharide [LPS] stimulated murine peritoneal macrophages. The inhibitory effect of auranofin and triethyl gold phosphine on LPS stimulated monokine production was reversible when these compounds were incubated with macrophage cultures at concentrations between 0.1-0.5 micrograms/ml. These compounds also inhibited both TNF and IL-1 production by human peripheral blood monocytes. Sodium aurothiomalate at these concentrations had no inhibitory effect on TNF or IL-1 production. Auranofin and triethyl gold phosphine also inhibited TNF production in vivo when compounds were administered orally or intraperitoneally 2 hours prior to a lethal dose of endotoxin. Serum TNF levels from Balb/c mice were significantly reduced when animals were predosed with 1-25 mg/kg of auranofin. The data suggest that the inhibition of TNF production by activated macrophages may contribute to the therapeutic role of gold compounds in the management of chronic inflammatory disease.
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PMID:Pharmacologic modulation of TNF production by endotoxin stimulated macrophages: in vitro and in vivo effects of auranofin and other chrysotherapeutic compounds. 250 10

We measured simultaneously circulating and cell-generated TNF-alpha and IL-1 after lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells (PBMC) by radioimmunoassay (RIA) in HIV-infected individuals at different stages of infection, classified according to CDC classification. TNF-alpha production, both in vitro and endogenous in sera, remained at the normal level in group II patients but was significantly increased in most patients in group IV (P less than 0.05). Most patients of group II and IV displayed normal level of IL-1 in their sera, whereas the level of this monokine generated in vitro was significantly reduced in both groups (P less than 0.05). The cytotoxic effect of factor(s) secreted by PBMC from HIV-infected individuals was evaluated towards a fibroblast cell line L929. The higher titre of cytotoxicity was directly related to a higher production of TNF-alpha by the cells from group IV patients and the effect could be removed by pre-absorption with anti-TNF-alpha monoclonal antibody.
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PMID:Production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) in patients with AIDS. Enhanced level of TNF-alpha is related to a higher cytotoxic activity. 261 49

Tumor necrosis factor-alpha (TNF), a monokine produced by lipopolysaccharide (LPS)-stimulated macrophages, is an activator of phagocytic functions and may modulate host responses during infection. To determine the effects of LPS on TNF activity and the pulmonary inflammatory response in vivo, we challenged rats systemically or intratracheally with LPS. Intravenous LPS significantly increased serum TNF content from nondetectable levels in control specimens to peak levels at 90 min, which declined to baseline by 3 h. In response to intratracheal LPS, levels of TNF both in bronchoalveolar lavage fluid and associated with alveolar macrophages increased significantly from near nondetectable levels in control animals. Increases in TNF levels were confined to the LPS-challenged compartment. Intravenous LPS resulted in a decrease in the number of peripheral blood neutrophils and in sequestration of these cells within the pulmonary vasculature. In contrast, intratracheal LPS elicited a marked intraalveolar inflammatory response.
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PMID:Compartmentalization of intraalveolar and systemic lipopolysaccharide-induced tumor necrosis factor and the pulmonary inflammatory response. 264 68

Although fibroblasts are important in providing a structural framework for most tissues, they also appear to be active participants in the inflammatory process via the production of specific mediators. The production of inflammatory mediators by fibroblasts is especially important in relation to their strategic location within connective tissue as they may act as a cellular communication bridge between the interstitium and vasculature. In this paper, we demonstrate that fibroblasts may participate in these inflammatory reactions by the production of a neutrophil chemotactic factor (NCF) with characteristics similar to a recently isolated and cloned monocyte-derived NCF. Either tumor necrosis factor-alpha-, interleukin-1 alpha-, or interleukin-1 beta-stimulated fibroblasts showed both a time- and dose-dependent increase in steady-state levels of NCF mRNA and secretion of chemotactic activity. In contrast, lipopolysaccharide and interleukin-6 failed to induce fibroblast-derived NCF. The expression of fibroblast-derived NCF mRNA was first detectable by 30 min poststimulation, whereas chemotactic activity was significantly observed 3-4 h postchallenge. Heat-inactivated monokine (100 degrees C) failed to induce NCF mRNA expression, suggesting that only the active proteins are capable of inducing NCF. Gel filtration analysis using high pressure liquid chromatography indicated peak chemotactic activity with an approximate molecular mass of 8000 daltons. This peak of NCF activity was found to be relatively stable to both heat and trypsin inactivation. Specificity of the fibroblast-derived neutrophil chemotactic activity was demonstrated with inhibition of chemotaxis by the addition of neutralizing antibody directed against recombinant human neutrophil chemotactic factor. These data provide evidence that monokine-treated fibroblasts can synthesize a potent chemotactic agent with molecular and physicochemical characteristics similar to monocyte-derived NCF and that this factor may contribute to neutrophil-mediated disease processes.
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PMID:Monokine-induced neutrophil chemotactic factor gene expression in human fibroblasts. 265 89

Nonlethal endotoxemia was produced in conscious fasted rats by the intravenous (i.v.) administration of Salmonella enteritidis lipopolysaccharide (LPS) at a dose of 30 micrograms/100 g together with the typical acute-phase response of fever at 4 hr post-LPS. Also at 4 hr post-LPS both hyperinsulinemia and hyperglucagonemia were manifested, the (insulin:glucagon) (I:G) molar ratio was not different from saline control animals, and normoglycemia was maintained. The monokine interleukin-1 (IL-1), which is synthesized de novo and then released by macrophages and monocytes following LPS phagocytosis, has been implicated in the typical responses to endotoxemia. Therefore, human natural IL-1 was injected i.v. at a dose of 50 U into conscious fasted rats. IL-1-induced fever occurred at 30 min postinjection. Hyperinsulinemia equal to two times the saline control value was also present at 30 min after monokine injection, with plasma insulin levels declining to below control values by 60 min and remaining depressed for up to 12 hr. In contrast, plasma glucagon concentrations were not significantly altered at any time between 15 min and 12 hr post-IL-1. Despite IL-1-elicited hyperinsulinemia with unchanged glucagon, which elevated the I:G molar ratio, normoglycemia was maintained after monokine administration. The coincident onset of fever and hyperinsulinemia at 30 min after i.v. administration of IL-1 suggests a common mediator for both responses.
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PMID:Hyperinsulinemia elicited by interleukin-1 and nonlethal endotoxemia in rats. 266 Oct 47

Hyperthermia in the therapeutic (greater than or equal to 42-43 degrees C) and febrile (less than or equal to 39-40.5 degrees C) ranges modulated the cytotoxic activities of macrophages cocultured with tumour cells and of the monokine tumour necrosis factor (TNF) against tumour cells. These modulatory interactions had clear treatment-sequence dependencies, and some sequences markedly augmented cytotoxic activities. Heated murine bacillus Calmette-Guerin-activated macrophages retained their cytotoxic activities better in coculture with unheated tumour cells if triggering with the endotoxin lipopolysaccharide preceded 1 h of heating at 42 or 43 degrees C than they did if heating to the same extent was concomitant with, or preceded, triggering. Retention of cytotoxicity in coculture during 24 h of 39 or 40.5 degrees C heating was less dependent on pre-heating triggering. The triggering/heating sequence also had modulatory effects on the secretion by heated macrophages of TNF which is involved in cytotoxic manifestations in coculture. Production of TNF by macrophages heated for 1 h at 40.5-43 degrees C or 24 h at 39 or 40.5 degrees C was augmented 1.5- to 6-fold (depending on the heat dose) when triggering preceded heating, whereas sequences in which heating was concomitant with triggering or preceded triggering were detrimental to TNF secretion. Profound treatment-sequence dependencies were also seen when timing of the addition of recombinant human TNF was varied in relation to the heat treatment of tumour cells. Sensitization of TNF-responsive L-929 and TNF-resistant EMT-6 tumour cells occurred if monokine addition preceded heating, whereas the reverse treatment-sequence reduced or eliminated sensitization. Both tumour cell types were also sensitized to TNF if monokine treatment preceded 24 h heating at 40.5 degrees C. These results support the hypothesis that appropriately constructed sequences for either macrophage priming/triggering or monokine treatment of tumour cells, combined with hyperthermia, could augment the cytotoxic actions of macrophages and the cytotoxicity of endogenously added monokines.
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PMID:Temporal dependence of hyperthermic augmentation of macrophage-TNF production and tumor cell-TNF sensitization. 267 Nov 83


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