Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour Necrosis Factor alpha (TNF/Cachectin) is a cytokine produced mainly by macrophages, which has been shown to cause endothelial cell damage, pyrexia and weight loss, clinical features of tuberculosis, but not of sarcoidosis which is in many other respects a similar disease. 1,25 di-hydroxy Vitamin D and gamma interferon, factors which are present in vivo in both tuberculosis and sarcoidosis, enhance the ability of macrophages to release TNF in vitro. We have studied the ability of pulmonary alveolar macrophages (PAM) harvested by broncho-alveolar lavage (BAL) to produce TNF in response to stimulation with E. coli endotoxin lipopolysaccharide (LPS). 25 patients undergoing bronchoscopy and BAL were studied: 9 with sarcoidosis, 7 with tuberculosis (TB) and 9 (non-neoplastic) disease controls. TNF was assayed by Enzyme Linked Immunosorbent Assay (ELISA) in lavage fluid and cell culture supernatants. No TNF was detected in lavage fluid from any of the groups. PAMs from control patients released no detectable TNF spontaneously, but released 59 +/- 31 units after LPS stimulation. Cells from patients with sarcoidosis and tuberculosis released TNF spontaneously in vitro (TB 226 +/- 106 units; Sarcoidosis 293 +/- 176). TNF release by these cells was not increased further by addition of an optimal concentration of LPS. Thus, the pulmonary macrophages of patients with sarcoidosis and tuberculosis released significantly more TNF than those of controls.
 ...
PMID:Tumour necrosis factor production by alveolar macrophages in pulmonary sarcoidosis and tuberculosis. 134 39

To determine whether the cytokine tumor necrosis factor/cachectin might be a mediator of hepatotoxicity seen after exposure to polyhalogenated aromatic hydrocarbons, rats treated with a single dose of 3,3',4,4'-tetrabromobiphenyl (150 mumol/kg intraperitoneally) or corn oil vehicle were studied. The 3,3',4,4'-tetrabromobiphenyl caused the expected anorexia, alterations in organ weights and changes in cytochromes P-450 over 21 days. Although tumor necrosis factor could not be detected in the serum of rats at any time after 3,3',4,4'-tetrabromobiphenyl treatment alone (from 90 min to 21 days), 3,3',4,4'-tetrabromobiphenyl treatment significantly increased peak serum tumor necrosis factor concentrations after intravenous bacterial endotoxin (lipopolysaccharide, 1 mg/kg). This effect was seen with lipopolysaccharide given 24 hr, 48 hr, and 20 days after 3,3',4,4'-tetrabromobiphenyl treatment and increases in peak serum tumor necrosis factor levels ranged from threefold to eightfold over controls in various experiments with no significant differences between the three time points. However, a synergistic increase in hepatic damage (assessed by serum enzymes and liver histological findings 24 hr after lipopolysaccharide injection) was seen in rats given lipopolysaccharide 24 hr and 48 hr after 3,3',4,4'-tetrabromobiphenyl administration, with 75% and 25% lethality, respectively. There was no lethality with lipopolysaccharide given 20 days after 3,3',4,4'-tetrabromobiphenyl administration or with simultaneous administration. A lower dose of lipopolysaccharide (0.1 mg/kg) given 24 hr after 3,3',4,4'-tetrabromobiphenyl also enhanced hepatotoxicity and serum tumor necrosis factor but without lethality. Lipopolysaccharide decreased cytochromes P-450 concentrations and activities to similar extents at all time points tested in both control and 3,3'4,4'-tetrabromobiphenyl-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:3,3',4,4'-Tetrabromobiphenyl sensitizes rats to the hepatotoxic effects of endotoxin by a mechanism that involves more than tumor necrosis factor. 166 20

Gram-negative septicemia remains one of the most serious forms of hospital-acquired infection. The most consistently virulent component of the gram-negative lipopolysaccharide (endotoxin) appears to be lipid A. Elucidation of the structure-function relationships of lipid A and the biochemical configurations required for endotoxicity makes possible the design of lipopolysaccharide antagonists and/or the production of poly- or monoclonal antibodies that may abrogate the biologic effects of endotoxin. The mechanisms of activity of lipopolysaccharide and the pathophysiologic events it triggers are now better understood than in the recent past. Lipid A triggers the release of mediators such as cachectin (tumor necrosis factor), thereby initiating a cascade of potentially lethal events. Although recent studies indicate no routine role for corticosteroids in gram-negative septic shock or acute respiratory distress syndrome, considerable progress has been made in the development of effective antibiotics. Recent studies of septicemia in neutropenic patients show survival rates significantly higher than those reported more than two decades ago.
 ...
PMID:University of California/Davis Interdepartmental Conference on gram-negative septicemia. 168 79

Although the shock syndrome is recognized as a form of "mediator poisoning", a plethora of details is hardly converging into a coherent concept of chronological and molecular order. As a model for organ failure in septic shock, three alternative experimental approaches with a common pathology are presented: When galactosamine-sensitized mice receive either lipopolysaccharide or leukotriene D4 or tumor necrosis factor alpha they develop fulminant hepatitis within few hours with a lethal outcome within one day. Detailed pharmacological intervention studies allow to conclude that endotoxin-induced leukotriene D4 release induces a transient ischemia by the known vasoconstrictive action of this eicosanoid. A following reperfusion/reoxygenation phase gives rise to superoxide formation which inactivates alpha 1 proteinase inhibitor. Thus a serine protease becomes active which is responsible for the processing of a monocytic tumor necrosis factor alpha precursor to be released into the circulation after proteolytic cleavage. By this sequence the final central mediator of shock and sepsis becomes systematically abundant. The concept arising from these studies reconciles previously known findings and provides a link between the role of reactive oxygen species in inflammation, the balance of proteases and antiproteases in the extracellular space and the release of the cytokine tumor necrosis factor in sepsis and shock.
 ...
PMID:Reactive oxygen species, antiproteases, and cytokines in sepsis. 179 93

The tumor necrosis factor, preliminary identified because of its antitumor properties, refers to two kinds of similar polypeptides (TNF or cachectin, and TNF-beta or lymphotoxin), which share some biological effects. Both substances, as members of the class of cytokines, play a role as mediators of inflammation and the cellular immune response. Human cachectin is produced as a prohormone and activated by cleavage of a 76 residue peptide. Mature cachectin (which comprises 157 amino acid residues) share a 28% amino acid sequence homology with lymphotoxin. Both cytokines are encoded by different genes of chromosome 6 and may compete for a common receptor. Cachectin is produced by a wide variety of cells (phagocytic and non-phagocytic), mainly by activated macrophages and monocytes. Different invasive stimuli (mainly lipopolysaccharide, a constituent of the Gram-negative bacteria's outer wall) activate cachectin biosynthesis, which is controlled chiefly at a post-transcriptional level. The newly synthetized cachectin remains associated as a transmembrane form, affecting their targets by direct cell-to-cell contact, or is actively secreted in the circulation to distant sites in the body, where it binds to high affinity cachectin receptor, on a variety of cell types. Cachectin exerts pleiotropic effects on normal, transformed, or tumoral cells. The biological effects mediate by cachectin may be beneficial or deleterious to the body, depending on the quantity produced, duration of cell exposure and further biochemical mediators in the environment of the target cells. Cachectin (frequently associated with severe infection and cancer) seems to be the result of a persistent exposure to raised levels of cachectin.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Biochemical characterization and metabolic effects of tumor necrosis factor]. 180 28

The role of cytokines in the development of acute graft-vs-host disease (GVHD) was investigated in B6AF1 mice that were injected with parental A/J lymphocytes. Splenocytes from GVH mice exhibited an increased capacity to produce interleukin (IL)-1, IL-6, and TNF-a when stimulated in culture with lipopolysaccharide (LPS). This enhanced capacity was diminished following in vivo treatment with immunosuppressive drugs. Concanavalin A-stimulated GVH spleen cells produced significantly lower levels of IL-2 but higher levels of interferon-gamma (IFN-gamma) than did syngeneic spleen cells. Immunosuppressive therapy in vivo increased the capacity of GVH spleen cells to produce IL-2. However, immunosuppressants differed in their effects on IFN-gamma production. Sch 24937 (6-bromo-5-chloro-2-[1-(methylsulfonyl)acetyl] 3-(2-pyridyl)indole) enhanced or had no effect while cyclosporin A consistently decreased the capacity of splenocytes to produce this lymphokine. These results indicate that the capacity of GVH splenocytes for cytokine production can be differentially affected by the actions of some pharmacological agents. The data also indicate that there may be differential regulation of the production of IL-2 and IFN-gamma by the Th1 subset in the GVH spleen.
 ...
PMID:A study of cytokine production in acute graft-vs-host disease. 190 99

The objective of this study was to investigate mechanisms by which polymorphonuclear neutrophils (PMNs) contribute to the tolerance induced by repeated lipopolysaccharide (LPS) injections. Tolerance was developed by daily intraperitoneal injections of sublethal doses of LPS for 4 days (LPS-tolerant group); controls were not pretreated (LPS-control group). Both groups were challenged with 9 mg/kg i.v. Escherichia coli LPS, a dose that resulted in 25% survival in LPS-control rats compared with 100% survival in LPS-tolerant rats. LPS injection caused an initial neutropenia in both groups. The neutropenia persisted throughout the experiment in LPS-control rats, whereas in LPS-tolerant rats the circulating PMN count increased dramatically; after 6 hours, the PMN count was 16-fold higher than that in LPS-control rats. Activation of circulating PMNs, PMN adhesion to nylon fibers, and tumor necrosis factor/cachectin activity were all increased in control rats given LPS. In contrast, LPS-tolerant rats had low activation of circulating PMNs, no trend for PMN adhesion to nylon fibers, and markedly reduced tumor necrosis factor activity. To determine whether neutropenia was associated with a trapping of PMNs in the microcirculation, we used a carbon perfusion technique 6 hours after LPS injection and examined histological sections of the myocardium. All of the arterioles and venules in both groups contained carbon; only capillaries showed evidence of obstruction. A significantly higher percentage of obstructed capillaries was observed in LPS-control rats than in LPS-tolerant rats. Obstruction of capillaries was consistently associated with trapped leukocytes. We conclude that PMN cytotoxicity induced by LPS involves microcirculatory entrapment and activation of PMNs. Repeated LPS pretreatment reduces dramatically circulating PMN activation and adhesion and is associated with an elevated circulating PMN count, a low degree of microvascular plugging, and survival after a normally lethal dose of LPS.
 ...
PMID:Polymorphonuclear neutrophil contribution to induced tolerance to bacterial lipopolysaccharide. 193 51

Cachectin-tumor necrosis factor (TNF-alpha) has been implicated as a possible signal for the initiation of human parturition in the setting of infection. These studies were conducted to determine whether human decidua can produce TNF-alpha in response to bacterial lipopolysaccharide (LPS). Decidual explants from women undergoing elective cesarean sections were incubated with and without Escherichia coli LPS (25 ng/ml) for 20 h. TNF-alpha concentration in the conditioned media was measured with an enzyme-linked immunoassay and bioassay (L929 bioassay). While conditioned media from unstimulated decidual explants contained either undetectable or low levels of TNF-alpha, conditioned media from LPS stimulated decidua contained TNF-alpha (mean = 2.6 pmol/mg protein per 20 hours, SEM +/- 1.03). There was a strong correlation between the immunoreactive and bioactive TNF-alpha (Spearman rank correlation r = 0.76, P less than 0.001). We conclude that human decidua in vitro can produce TNF-alpha in response to LPS.
 ...
PMID:Human decidua: a source of cachectin-tumor necrosis factor. 193 92

The effect on food intake, body weight, and survival of mice given recombinant lipopolysaccharide (LPS), tumor necrosis factor/cachectin (TNF), or interleukin 1 (IL-1) (5 micrograms/mouse, ip, twice daily) was studied. All agents induced a rapid reduction of food intake and body weight after 1 day of treatment. Unlike TNF and LPS, IL-1 given as two daily administrations of 5 micrograms was lethal within 3 days. Mice treated with LPS or TNF rapidly developed tolerance to their anorectic effect, whereas tolerance to IL-1 required a longer time to develop and was not complete. We investigated the possible roles of changes in serum corticosterone and glucose in the effects of LPS, TNF and IL-1. A single injection of LPS, TNF, or IL-1 markedly increased serum corticosterone levels after 2 h. After only 2 days of chronic treatment, mice given LPS or TNF were refractory to induction of serum corticosterone by a subsequent injection of LPS or TNF, but mice given IL-1 for 2 days were still fully responsive to IL-1. IL-1, unlike TNF and LPS, induced a marked hypoglycemic response. Repeated administration of IL-1 sensitized to its hypoglycemic effect. This lack of adaptation to the increase of serum corticosterone and hypoglycemia was also observed when IL-1 was given at lower, nonlethal doses (0.25-1.0 microgram) and for a longer period (up to 8 days). The defective tolerance to the metabolic and toxic effects of IL-1 in this experimental model indicates that there are major differences between the in vivo biological responses to IL-1 and TNF.
 ...
PMID:Defective tolerance to the toxic and metabolic effects of interleukin 1. 199 79

Wasting and secretion of the catabolic cytokines tumor necrosis factor (TNF)/cachectin and interleukin 1 (IL-1) were assessed in weanling Syrian hamsters infected with Leishmania donovani amastigotes. Whereas the mean weight of uninfected animals increased progressively over 9 weeks, the mean weight of infected animals plateaued at 4-6 weeks and then decreased progressively until death. Splenic mononuclear cells from control hamsters produced 11.3 +/- 8.3 (SD) ng TNF/10(6) mononuclear cells/24 hr. TNF secretion in infected animals was greater than the mean +/- 2 SD of controls in 1 of 3 hamsters at 2 weeks post-infection and in 8 of 9 hamsters at weeks 4-8. The mean TNF secreted by infected animals studied at weeks 4-8 was 371 (range 28-800) ng TNF/10(6) mononuclear cells/24 hr (P = 0.005). Control hamsters produced 7.7 +/- 2.7 pg IL-1/10(6) mononuclear cells/24 hr. At 2 weeks, mononuclear cells from 2 of 3 infected animals secreted amounts of IL-1 greater than the mean +/- 2 SD of controls. All of 8 infected hamsters secreted increased amounts of IL-1 at 4-8 weeks. The mean was 164 (range 17-370) pg IL-1/10(6) mononuclear cells/24 hr (P = 0.002). In comparison to infected animals, mononuclear cells from control hamsters incubated with lipopolysaccharide, 10 micrograms/ml, produced 172.5 ng TNF and 44.6 pg of IL-1/10(6) mononuclear cells/24 hr. The effect of visceral leishmaniasis on food intake was assessed in a separate group of animals housed individually in metabolic cages. Significant reductions in weight and food intake were first observed at 2 and 3 weeks of infection, respectively. By 5 weeks, the food intake of infected animals was 46% that of controls. Syrian hamsters infected with L. donovani provide an excellent model with which to study the mechanism of wasting.
 ...
PMID:Wasting and macrophage production of tumor necrosis factor/cachectin and interleukin 1 in experimental visceral leishmaniasis. 226 69


1 2 3 4 5 6 7 8 9 Next >>