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 human acute phase protein, C-reactive protein (CRP), is capable of specifically binding to and modulating the function of mononuclear phagocytes. To investigate whether CRP can also affect the capacity of these cells to produce inflammatory cytokines, enzyme immunoassays and Western blot techniques were used to quantitate interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) produced by freshly-isolated normal human monocytes. CRP induced the rapid release of each cytokine, with significantly elevated levels in culture supernatants at 4 hours and maximal levels of TNF-alpha at 8 hours, and of IL-1 beta and IL-6 at 16 hours of culture. The effects of CRP were dose-dependent; greater than 10-fold increases of each cytokine were observed following culture with greater than or equal to 50 micrograms/ml CRP, concentrations which are often found in the presence of moderate to severe inflammation or tissue injury. The induction of cytokine release by CRP was unaffected by inclusion of 25 micrograms/ml polymyxin-B in culture media, but was completely abrogated by prior boiling of the CRP, a procedure which had no effect on induction of monocyte cytokine release by lipopolysaccharide. The dose-dependent induction of inflammatory cytokines by CRP provides further support for the hypothesis that interaction with mononuclear phagocytes constitutes an important biological role for this acute phase protein.
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PMID:Induction of inflammatory cytokine release from cultured human monocytes by C-reactive protein. 142 Sep 97

The hepatic production of the acute phase proteins in response to inflammatory cytokines, and the interaction of corticosteroids within this response, has been the subject of considerable recent research. In this study we have examined the effects of the corticosteroid prednisolone on the production of IL-1 alpha and IL-1 beta by lipopolysaccharide (LPS)-stimulated monocytes, and the ability of the monocyte conditioned media (MOCM) obtained under these conditions to induce human hepatoma HepG2 cells to produce serum amyloid A (SAA) and C-reactive protein (CRP). We also examined the production of SAA and CRP by HepG2 cells exposed to different combinations and concentrations of recombinant human (rh) IL-1 alpha, rhIL-1 beta, rhIL-6, recombinant human tumour necrosis factor-alpha (rhTNF-alpha) and prednisolone. The findings indicate: (i) prednisolone substantially inhibits the production of both IL-1 alpha and IL-1 beta by LPS-stimulated monocytes. The MOCM from prednisolone-treated monocytes induced less SAA and CRP production by HepG2 cells; (ii) IL-1 alpha and IL-1 beta both induced CRP and SAA synthesis by HepG2 cells, but only in the presence of IL-6. IL-1 beta was the more potent inducer for SAA production, but for CRP production IL-1 alpha and IL-1 beta were equivalent; (iii) prednisolone enhances the production of SAA by HepG2 cells, but does not enhance the production of CRP; (iv) TNF-alpha in the presence or absence of IL-6 and/or prednisolone did not induce the production of SAA or CRP by HepG2 cells. These findings offer a tenable solution to a disparate production of SAA compared with CRP in corticosteroid-treated cystic fibrosis (CF) patients.
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PMID:Production of serum amyloid A and C-reactive protein by HepG2 cells stimulated with combinations of cytokines or monocyte conditioned media: the effects of prednisolone. 142 89

Inhalation of 20 micrograms endotoxins (from the membrane of Gram-negative bacteria) has been reported to induce a bronchial obstructive response in asthmatic subjects. The aim of the present study was to evaluate in asthmatic patients the possibility of an inflammatory response to inhaled endotoxins. Eight patients with mild asthma were submitted to bronchial challenge tests, in a single-blind trial, on Day 1 with control solution and on Day 7 with 20 micrograms endotoxin of Escherichia coli (026:B6). Local inflammatory response was indirectly evaluated by the degree of bronchial hyperresponsiveness (BHR) expressed as PD20 FEV1 histamine (the dose of histamine inducing a 20% decrease in FEV1) at 0, 6, 24, and 48 h and 7 days. Systemic inflammation was investigated by sequential blood determinations of total (and differential) white cells, complement anaphylatoxin C5a, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP). A significant (p < 0.01) bronchial obstructive response was demonstrable 45 min after lipopolysaccharide (LPS) inhalation, lasting 5 h. Comparing the level of BHR after control inhalation, a significant (p < 0.05) increase in BHR was shown 6 h after LPS, partially normalized at 24 and 48 h. A short peak in TNF-alpha at 60 min (p < 0.05) and an increase in total white blood cells (p < 0.01) and neutrophil polymorphonuclear neutrophils at 360 min (p < 0.05) and of CRP at 24 and 48 h (p < 0.05 and p < 0.01) were significant. The other blood parameters did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inflammatory response to acute inhalation of endotoxin in asthmatic patients. 148 24

This study sought to determine whether endogenous tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte-colony-stimulating factor (G-CSF) were detectable in sera of lipopolysaccharide (LPS)-treated cancer patients. Twenty patients received an intravenous bolus of purified LPS from Salmonella abortus-equi (4.0 ng/kg). Patients were pretreated with ibuprofen (1,600 mg) to prevent constitutional side effects like fever and chills. Serum TNF-alpha levels increased from less than 0.01 ng/ml before treatment up to maximal levels of 21 ng/ml, peaking 1.5 h after LPS injection. Similarly, serum IL-6 concentrations increased from less than 0.01 to 11 ng/ml, but peak levels were obtained 30 min later than TNF-alpha. Circulating G-CSF appeared still later than TNF-alpha and IL-6. It was detectable within 3 h and peaked 6 h after LPS injection. Parallel to the release of the above cytokines a marked increase in granulocyte counts was observed. In all patients administration of LPS led to an acute-phase response as measured by C-reactive protein.
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PMID:Treatment of cancer patients with endotoxin induces release of endogenous cytokines. 171 15

The fetal and maternal concentration of various plasma proteins alters during pregnancy. Cells in the livers of fetal hamsters accumulate serum amyloid A (SAA) and C-reactive protein (CRP) mRNA, major acute phase reactants, when lipopolysaccharide is administered to the fetal circulation. No fetal SAA or CRP mRNA response is seen when the mother is stimulated at a remote site by endotoxin or a nonspecific inflammatory agent. In addition, cells of the fetal hamster liver do not respond by accumulating SAA mRNA when exposed to the specific cytokines, tumor necrosis factor, IL-1, and IL-6. CRP mRNA levels increased in fetal livers after administration of tumor necrosis factor and IL-1. These data suggest that cells contained in the fetal liver can respond during an acute phase reaction but that the capacity of some acute phase reactant genes to respond to cytokines may be developmentally regulated. Studies of immature hamsters after birth show that the responses of CRP and SAA genes to lipopolysaccharide, tumor necrosis factor, IL-1, and IL-6 are reduced when compared with induction of mRNA accumulation for these acute phase reactants in adult animals.
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PMID:Developmental regulation of expression of C-reactive protein and serum amyloid A in Syrian hamsters. 175

The cytokine interleukin-1 plays an important role in the production and modulation of the immune response in rheumatoid arthritis. It is produced by macrophages of the inflamed synovial tissue and induces the autocrine production of interleukin-1, amplifies the T-cell dependent immune response and has potent effects on inflammatory reactions of many non-lymphoid cell-systems. By means of a sensitive and specific ELISA interleukin(Il)-1 beta was measured in the peripheral blood and synovial fluid of patients with rheumatoid arthritis in comparison to controls in significantly increased levels (medium values: 280 pg/ml and 325 pg/ml versus less than 20 pg/ml). The Il-1 beta concentrations in the peripheral blood and in the synovial fluid were well correlated, but there was no correlation to other inflammation parameters like erythrocyte sedimentation rate or C-reactive protein, however, a good correlation to the nephelometrically measured rheumatoid factor (r = 0.71). In twelve hour cultures of adherent cells significantly increased spontaneous intracellular Il-1 beta-production was determined in synovial fluid macrophage cultures of rheumatoid arthritis patients compared to peripheral blood monocyte cultures of controls (median values 91.0 ng/10(6) cells versus 31.5 ng/10(6) cells). The secretion into the culture supernatant has to be stimulated by additional lipopolysaccharide. Interferon-gamma inhibits the spontaneous intracellular Il-1 beta-production of synovial fluid macrophages from rheumatoid arthritis patients. These findings may be of importance for the effect of the interferon-gamma therapy in the treatment of rheumatoid arthritis.
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PMID:[Interleukin-1 in the pathogenesis of chronic polyarthritis]. 211 62

Induction of C-reactive protein (CRP) by conditioned medium from lipopolysaccharide-stimulated human monocytes in two human hepatoma-cell lines, Hep 3B and NPLC/PRF/5, was potentiated 3-6-fold by the methylxanthine caffeine. The induction observed in the presence of conditioned medium plus caffeine was as much as 180-fold, comparable with that seen after many stimuli in vivo. This potentiation was accompanied by an increase in the levels of CRP mRNA. By contrast, no potentiating effect on CRP induction by conditioned medium was found when we tested theophylline, forskolin, 8-bromo cyclic AMP or two Ca2+ ionophores, namely ionomycin and A23187. None of the above compounds, including caffeine, when tested alone, had any detectable effect on the synthesis and secretion of CRP. Our previous study [Ganapathi, May, Schultz, Brabenec, Weinstein, Sehgal & Kushner (1988) Biochem. Biophys. Res. Commun. 157, 271-277], employing defined cytokines, had shown that induction of CRP in Hep 3B cells requires IL(interleukin)-6 plus IL-1, whereas, in the NPLC/PRF/5 cell line, IL-6 alone is effective. Caffeine similarly potentiated induction of CRP by these defined cytokine signals in these two cell lines. Changes in synthesis of other acute-phase proteins, including serum amyloid A (SAA), alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin and albumin, induced by conditioned medium or, in some cases, by IL-6 and/or IL-1 alpha, were only minimally affected by caffeine. Thus these results indicate that the mechanism by which caffeine potentiates CRP induction by cytokines appears to be independent of increases in intracellular concentrations of the two second messengers, cyclic AMP and Ca2+; the precise nature of this mechanism is unclear at the present time. Our results also indicate that the intracellular mechanisms by which cytokines regulate synthesis of CRP may differ from those regulating synthesis of some other acute-phase proteins. The differential response of CRP and SAA to caffeine is of particular interest, since induction of both of these two major acute-phase proteins can be accomplished by identical extracellular signals.
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PMID:Induction of C-reactive protein by cytokines in human hepatoma cell lines is potentiated by caffeine. 216 98

The purpose of the study was to evaluate the toxicity and biological activity of highly purified lipopolysaccharide (LPS) administered intravenously to cancer patients in order to establish an optimum dosage scheme. An initial subtoxic dose was increased in weekly increments in accordance with individual regimens that maintained patient reaction at a safe and acceptable level. Purified LPS from Salmonella abortus equi was administered to 11 patients with advanced solid tumors on a weekly schedule with intraindividually escalating dosage as determined by patient response. Biological response was monitored by complete blood count, C-reactive protein, and cytokine measurements at different time points after LPS injection. Tumor necrosis factor-alpha (TNF) and interleukin-1 beta serum levels were measured by enzyme-linked immunosorbent assay and interleukin-6 (IL-6) by bioassay. Dose-limiting toxicities including chills and fever (WHO grade III) were reached at 1.0 ng/kg of body weight (maximal tolerated dose-1, MTD-1). Pretreatment with ibuprofen (1,600 mg) abrogated these side effects, allowing further escalation of LPS doses up to 10 ng/kg of body weight. At dose levels greater than 8.0 ng/kg of body weight (MTD-2), the aforementioned side effects occurred again and, additionally, hepatic toxicity (WHO grade III) was observed. Hematological changes included neutropenia followed by a pronounced neutrophilia contributed to by up to 30% bands, marked monocytopenia for 3 h, and retarded lymphopenia. By 24 h, all hematological parameters returned to pretreatment values. TNF serum levels increased from 10 pg/ml before treatment to 7,000 pg/ml as a function of dosage. Maximum serum levels were reached at 60 to 90 min after LPS injection. Similarly, IL-6 serum concentrations increased from less than 4 to 2,500 U/ml; peak levels were obtained 30 min after TNF peak values. Prior administration of ibuprofen had no effect on the above-mentioned hematological changes nor on cytokine release. LPS can be administered intravenously in weekly intervals at escalating doses from 0.15-10.0 ng/kg of body weight, when patients are protected by pretreatment with ibuprofen at dose levels above 1.0 ng/kg of body weight. Cytokine release as measured by TNF and IL-6 increased in a dose-dependent manner although the constitutional symptoms are completely attenuated.
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PMID:Biological response to intravenously administered endotoxin in patients with advanced cancer. 225 60

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

We measured the plasma concentrations of factor VIII procoagulant (FVIII:C) in rabbits in two laboratory models of inflammation and after injections of purified homologous interleukin 1 (IL-1). The mean FVIII:C activities 2-4 days following the intramuscular injection of turpentine were significantly elevated, as were the concentrations of fibrinogen and C-reactive protein (CRP). By contrast, rabbits given 50 ng of bacterial lipopolysaccharide intravenously developed increased levels of FVIII:C but not of fibrinogen or CRP. We then studied plasma levels of FVIII:C, fibrinogen, and CRP after injections of either form of purified rabbit IL-1. If the rabbits' temperatures were monitored, FVIII:C levels increased in a log dose-related manner. This effect was not seen unless the rabbits were restrained and was seen in restrained rabbits even if the temperatures were not monitored. Fibrinogen and CRP levels did not change after IL-1 injections. These findings demonstrate that FVIII:C is an acute-phase reactant as judged by its response to turpentine inflammation or endotoxin injections, and to injections of IL-1 in restrained rabbits. FVIII:C appears to be a more sensitive acute-phase reactant than either fibrinogen or CRP. Neither of the latter proteins responded to low-dose endotoxin injections nor to either form of purified homologous IL-1. The doses of IL-1 given did cause fever, neutrophil leukocytosis, and hypoferremia.
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PMID:Acute-phase behavior of factor VIII procoagulant and other acute-phase reactants in rabbits. 247 59


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