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)

An interleukin 1 alpha (IL-1 alpha) cDNA probe and an IL-1 responsive T-cell clone (D10.G4; half-maximal stimulation, 0.1-1 pM) have been used to study the production of IL-1 by primary murine cell populations, particularly macrophages and dendritic cells. Spleen and peritoneal macrophages produced IL-1 mRNA and released biologically active IL-1 when challenged with lipopolysaccharide (LPS). Induction of IL-1 was evident over a dose range of 0.01-10 micrograms of LPS per ml, and maximal mRNA levels were maintained from 4 to 20 hr. Several other stimuli did not induce IL-1 in cultured macrophages, including phorbol 12-myristate 13-acetate, gamma-interferon, Con A, macrophage colony-stimulating factor, IL-3, cachectin, and activated T cells. Activated T cells could markedly reduce the response of peritoneal macrophages to LPS. When other cell types were compared with macrophages, keratinocytes had high levels of IL-1 mRNA, apparently in response to endogenous LPS. However B and T lymphocytes did not yield detectable IL-1 during proliferative responses to LPS and Con A, respectively, while dendritic cells produced little or no IL-1 when challenged with a battery of stimuli. Therefore, IL-1 may not be required for the potent accessory function of dendritic cells in lymphocyte mitogenesis. The results indicate that macrophages and dendritic cells have different secretory capacities. The macrophage is the principal leukocyte that synthesizes IL-1, and select stimuli increase and decrease the levels of macrophage IL-1 mRNA.
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PMID:Induction of murine interleukin 1: stimuli and responsive primary cells. 349 97

A highly specific polyclonal rabbit antiserum directed against murine cachectin/tumor necrosis factor (TNF) was prepared. When BALB/c mice were passively immunized with the antiserum or with purified immune globulin, they were protected against the lethal effect of the endotoxin lipopolysaccharide produced by Escherichia coli. The prophylactic effect was dose-dependent and was most effective when the antiserum was administered prior to the injection of the endotoxin. Antiserum to cachectin/TNF did not mitigate the febrile response of endotoxin-treated animals, and very high doses of endotoxin could overcome the protective effect. The median lethal dose of endotoxin in mice pretreated with 50 microliters of the specific antiserum was approximately 2.5 times greater the median lethal dose for controls given nonimmune serum. The data suggest that cachectin/TNF is one of the principal mediators of the lethal effect of endotoxin.
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PMID:Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. 389 37

Endotoxin-induced cells of the reticuloendothelial system were shown to produce mediator(s) that evoke a state of cachexia in recipient animals. The factor(s) responsible were assayed in endotoxin-resistant (C3H/HeJ) mice, which were injected with dialyzed conditioned medium obtained from lipopolysaccharide-induced peritoneal macrophages. The mice exhibited weight loss and anorexia, and they died if sufficient quantities of medium were administered. The syndrome was reversible if injections were discontinued. Endotoxin alone did not produce this effect, and no gross pathologic lesions were discernable in the treated animals. In this model system, cachexia appears to result from the action of soluble macromolecules produced by activated macrophages in vitro. Cachectin (murine tumor necrosis factor) is thought to play a central role in this phenomenon.
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PMID:Weight loss associated with an endotoxin-induced mediator from peritoneal macrophages: the role of cachectin (tumor necrosis factor). 391 May 66

The appearance of endogenously produced inhibitors against tumor necrosis factor (TNF) (soluble TNF-receptor type I, sTNFR-I) and interleukin-1 (IL-1 receptor antagonist, IL-1ra) was evaluated acutely in five normal patients after experimental endotoxemia lipopolysaccharide (LPS) and prospectively during a one to 11 week period in 12 septic, critically ill patients. Increased levels of both factors remained detectable in the circulation for up to 24 hours after LPS (2 nanograms per kilogram body weight) administration in normal patients. Despite free TNF-a activity being detected only sporadically (3 percent of the samples) and that IL-1 beta was never detectable in the patients in the intensive care unit, IL-6 bioactivity was present in 90 percent of initial samples. Circulating sTNFR-I levels up to 62,000 picograms per milliliter and IL-1ra levels of 14,800 picograms per milliliter were noted in the critically ill patients and remained consistently detectable throughout the extended period of evaluation. While there was no difference in IL-1ra levels between patients who survived or ultimately died, sTNFR-I levels were significantly (p < 0.001) lower in survivors compared with nonsurvivors. A correlation between circulating sTNFR-I and concurrent cortisol levels (r = 0.64; p < 0.002) was also noted. Furthermore, a correlation between sTNFR-I and the severity of initial insult, as assessed by APACHE II scores (r = 0.54; p < 0.01) was demonstrable. These naturally occurring cytokine antagonists likely represent additional indicators of the presence of an infectious or other inflammatory process and seem to persist in the circulation even during conditions in which their respective proinflammatory cytokines are not demonstrable.
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PMID:Persistently elevated soluble tumor necrosis factor receptor and interleukin-1 receptor antagonist levels in critically ill patients. 817 22

The effects of tumor necrosis factor-alpha (TNF-alpha; cachectin) and lipopolysaccharide of Salmonella enteritidis (LPS; endotoxin) on leucine metabolism in rats were evaluated in the whole body using intravenous infusion of L-[1-14C]leucine and in isolated perfused liver (IPL) using the single-pass perfusion technique with alpha-keto[1-14C]isocaproate as a tracer for measurement of ketoisocaproic acid (KIC) oxidation, and the recirculation technique for measurement of hepatic amino acid exchanges. The data obtained in TNF-alpha and LPS groups were compared with those obtained in controls. Both TNF-alpha and LPS treatment induced an increase of whole body leucine turnover, oxidation, and clearance. As the result of a higher increase of leucine oxidation than of incorporation into the pool of body proteins, the fractional oxidation of leucine was increased. The fractional rate of protein synthesis increased significantly in the spleen (both in TNF-alpha and LPS rats), in blood plasma, liver, colon, kidneys, gastrocnemius muscle (in LPS rats), and in lungs (TNF-alpha-treated rats), whereas it decreased in the jejunum (LPS rats). In IPL of TNF-alpha- and LPS-treated rats a decrease of KIC oxidation and higher uptake of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) were observed when compared with control animals. We hypothesize that the negative consequences of increased whole body proteolysis and of increased oxidation of BCAA induced by TNF-alpha and/or LPS are reduced by decreased activity of hepatic branched-chain ketoacid dehydrogenase that can help resupply BCAA to the body.
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PMID:Leucine metabolism in TNF-alpha- and endotoxin-treated rats: contribution of hepatic tissue. 943 18

Antibody (Ab) responses to i.m. administered SRBC and BSA, and i.p. administered Escherichia coli lipopolysaccharide (LPS), and BW at various times after treatment, were measured in chicken lines divergently selected for high (H) and low (L) Ab responses to SRBC, and in a randombred control line (C). The Ab responses to SRBC and BSA, but not LPS, were significantly affected by line by treatment interactions. Levels of antibodies to SRBC and BSA were higher in the H line than in either the C or L line (P < 0.05). Administration of LPS did not affect Ab responses to SRBC, but Ab responses to BSA were decreased in birds that received BSA and LPS simultaneously. Body weights of C and L lines were significantly higher than BW of H line birds at all times. Lipopolysaccharide injection induced an acute, but transient reduction of BW gain, which was not affected by line. Antibody responses to SRBC and BSA were negatively correlated with BW. During the experimental period, however, percentage BW gain and humoral responsiveness were positively correlated. A higher percentage BW gain growth was seen in H line birds at the end of the experimental period. The present results confirm the hypothesized acute cachectin nature of LPS, but the relationship between live BW (gain) and immune responsiveness in chickens remains to be further clarified.
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PMID:Antibody responses and body weights of chicken lines selected for high and low humoral responsiveness to sheep red blood cells. 1. Effect of Escherichia coli lipopolysaccharide. 949 89

Previously we have established a clonal squamous cell carcinoma cell line OKa-C-1 derived from lung cancer of a patient with marked leukocytosis and hypercalcemia. OKa-C-1 cells simultaneously produce granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) at the single cell level and cause paraneoplastic syndromes in nude mice bearing the tumor. It is known that the production of G-CSF and PTHrP is individually regulated by inflammatory cytokines in various malignant cells. To investigate the common factors in the regulation of G-CSF and PTHrP production in OKa-C-1 cells, we examined the effects of some inflammatory agents [lipopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) beta and IL-6] on G-CSF and PTHrP production, by means of enzyme-linked immunosorbent assay (ELISA), immunoradiometric assay (IRMA) and quantitative reverse transcription-polymerase chain reaction (RT-PCR). TNF-alpha or IL-1beta induced both G-CSF and PTHrP production in the conditioned medium. TNF-alpha synergized with IL-1beta to significantly increase G-CSF production. In addition, TNF-alpha and IL-1beta strongly induced G-CSF mRNA with peaks at 2 and 6 h respectively. Although PTHrP production was also strongly induced by TNF-a PTHrP mRNA expression was more strongly induced by PMA than by TNF-alpha. Thus, TNF-alpha and IL-1beta could be common factors that individually and synergistically regulate G-CSF and PTHrP production in OKa-C-1 cells. Moreover, G-CSF and PTHrP production could be not only transcriptionally, but also posttranscriptionally regulated by other factors.
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PMID:Regulation of granulocyte colony-stimulating factor and parathyroid hormone-related protein production in lung carcinoma cell line OKa-C-1. 1101 Nov 19

Hemorrhagic shock results in a severe impairment of the immune response. Immunological alterations after hemorrhagic shock thus appear to be responsible for reduced resistance to infectious agents commonly observed after shock and severe injury. In the present study we examined the TNF-alpha-producing capacity of immune cells derived from different organs after sublethal shock in rats. Hemorrhagic shock was established by pressure controlled bleeding to a mean arterial pressure of 35 mm Hg for 35-40 min and consecutive resuscitation in male Sprague-Dawley rats. Twenty four hours after shock, TNF-a production in response to lipopolysaccharide (LPS, Salmonella friedenau) stimulation was measured in isolated spleen, bone marrow and blood cells. TNF-a production could be induced by stimulation with 1 ng/ml, in blood, spleen and bone marrow cells collected from sham-operated animals. A maximal stimulation was observed in all cell types after stimulation with 10 ng/ml LPS and could not be further increased with LPS doses of 100 ng/ml. Hemorrhagic shock of 35 mm Hg for 35-40 min, with consecutive resuscitation did not result in mortality, in contrast to a 4 hours lasting hemorrhagic shock resulting in 80% mortality. Blood, spleen or bone marrow cells, harvested from animals 24 hours after sublethal hemorrhagic shock, showed a significantly reduced TNF-alpha production in all cell populations after LPS stimulation. Serum collected from animals 2 hours after sublethal hemorrhagic shock contained an activity not present either before or 24 hours after shock, that downregulated LPS-induced TNF-alpha production in rat whole blood cultures and the murine macrophage cell line J774. The inhibitory activity present in serum, 2 hours after shock is not IL-10 since this mediator was not detectable in any serum sample. However, in the serum samples with TNF-alpha-inhibitory activity, elevated levels of PGE2 metabolites were found, which suggests the involvement of prostaglandins in trauma-induced immunosuppression. Altered TNF-a expression might be partially explained by an inhibitory activity in the serum already present 2 hours after shock. Since adequate, but not overwhelming TNF-alpha production is essential for host response, the altered cytokine formation might explain local and systemic susceptibility to infections after hemorrhagic shock.
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PMID:Sublethal hemorrhagic shock reduces tumor necrosis factor-alpha-producing capacity in different cell compartments. 1102 27

Cultured murine macrophages (RAW 264.7) were used to evaluate the temporal relationships between cytotoxicity, phagocytosis, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production, and alterations in expression of stress proteins after exposure to cadmium oxide (CdO) or cadmium chloride (CdCl(2)), particulate and soluble forms of cadmium, respectively. Macrophages were exposed in vitro to CdO (25 or 50 microg) or CdCl(2) (30 or 40 microM) for 2 to 72 h. Cytotoxicity was not evident until 18 h when exposed to 30 microM CdCl(2) or 25 microg CdO, but occurred as early as 12 h after exposure to 40 microM CdCl(2) or 50 microg CdO. Relative to untreated controls, phagocytic activity decreased progressively from 2 to 24 h after exposure to both forms of cadmium. TNF-alpha levels increased to 2- to 3-fold after 4 h and remained elevated until 24 h after exposure to 25 and 50 microg CdO and 30 microM CdCl(2), but decreased by 18-24 h at 40 microM CdCl(2). CdCl(2) or CdO alone did not induce NO; however, both cadmium species reduced lipopolysaccharide (LPS)-stimulated NO production in a dose-dependent manner. Enhanced de novo synthesis of 70- and 90-kD heat shock, or stress, proteins was observed 2 to 8 h after exposure to both CdCl(2) and CdO; however, synthesis of these proteins returned to control levels by 24 h. Stress protein synthesis was enhanced by CdCl(2) or CdO prior to cytotoxicity, but coincided with a decrease in phagocytic capacity and an increase in TNF-a levels. The data suggest that cultured macrophages respond similarly in vitro to a particulate form and a soluble form of cadmium in a cell type that plays a pivotal role in inflammatory and immune responses.
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PMID:Effects of particulate and soluble cadmium species on biochemical and functional parameters in cultured murine macrophages. 1103 23

This experiment was undertaken to determine the role of macrophage-derived nitric oxide (NO) in mediating lipopolysaccharide (LPS)-induced bone resorption by using an in vitro co-culture system and an in vivo model of infectious bone resorption. Our results demonstrated that LPS stimulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-a mRNAs and nitrite synthesis in the J774 mouse macrophage cell line but not in the UMR-106 (rat) and MC3T3-E1 (mouse) osteoblast cell lines. Conditioned media (CM) from LPS-stimulated J774 triggered only low to moderate levels of iNOS mRNAs in MC3T3-E1 and a trivial effect in UMR-106. On the other hand, CM induced matrix metalloproteinase-1 (MMP-1) gene expression in both osteoblast cell lines. The NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) did not alter this effect in MC3T3-E1 and UMR-106, whereas TNF-a antibody diminished the CM-induced MMP-1 gene expression in both cell lines. Interestingly, SNAP, a NO donor, although by itself is not a MMP-1 stimulator for UMR-106, augmented the TNF-alpha-stimulated MMP-1 mRNA production in UMR-106. In a J774/UMR-106 co-culture system, LPS stimulated significant MMP-1 gene expression in UMR-106, and this upregulation was abolished by L-NMMA and TNF-alpha antibodies. Immunohistochemical analysis in a rat model of infectious bone resorption (periapical lesion) showed co-distributions of iNOS+ macrophages and MMP-1+ osteoblasts around the osteolytic areas. Administration of L-NMMA markedly reduced the extent of bone loss and the percentage of MMP-1-synthesizing osteoblasts. These data suggest that NO derived from macrophages after LPS stimulation may enhance bone loss by augmenting the cytokine-induced MMP-1 production in osteoblasts.
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PMID:Nitric oxide promotes infectious bone resorption by enhancing cytokine-stimulated interstitial collagenase synthesis in osteoblasts. 1251 Aug 4


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