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)

Macrophages collected from BCG-infected mice or exposed in vitro to interferon-gamma plus lipopolysaccharide developed a cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. This trypanostatic activity of activated macrophages was inhibited by addition of N-monomethyl-L-arginine, an inhibitor of the L-arginine-nitric oxide (NO) metabolic pathway, indicating a role for NO as the effector molecule. Contrary to trypanosomes treated with N2gas, trypanosomes treated with NO gas did not proliferate in vitro on normal macrophages. Compared to mice infected with control parasites, mice infected with NO-treated parasites had decreased parasitemias in the first days postinfection and had a prolonged survival. Addition of excess iron reversed the trypanostatic effect of both activated macrophages and NO gas. These data show that activated macrophages exert an antimicrobial effect on T.b. gambiense and T.b. brucei through the L-arginine-NO metabolic pathway. In trypanosomes, NO could trigger iron loss from critical targets involved in parasite division. The participation of this effector mechanism among the other immune elements involved in the control of African trypanosomes (antibodies, complement, phagocytic events) remains to be defined.
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PMID:Nitric oxide-mediated cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. 142 37

The efficacy of the water-soluble derivative (WSD) of natural propolis (bee glue) was examined for augmentation of host resistance against experimental infections caused by Gram-negative pathogens (Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa). The substance was found to induce significant non-specific protection, but did not inhibit the in vitro growth of the same strains. Pretreatment with WSD prior to the standard scheme for tumour necrosis factor (TNF) induction (BCG and two weeks later lipopolysaccharide (LPS)) provoked an interval-dependent reduction in the lytic capacity of serum against L 929 target cells. The replacement of the triggering or priming signal with WSD markedly increased TNF production. In vivo administration of WSD led to a rapid and route-dependent change in the alternative complement pathway haemolysis. The alteration in C1q complement component and total protein synthesis, and also in nitroblue tetrazolium reduction, suggests that macrophage activation makes a major contribution to the capacity of WSD to prevent infections.
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PMID:Immunomodulatory action of propolis: IV. Prophylactic activity against gram-negative infections and adjuvant effect of the water-soluble derivative. 145 7

The ability of orally administered Deodan, a product from the cell wall of Lactobacillus bulgaricus strain "I. Bogdanov patent strain tumoronecroticance B51" ATCC #21815, shortly called "LB51", to induce endogenous tumor necrosis factor-alpha (TNF alpha) production in normal mice was evaluated. The priming and triggering activities of the preparation were investigated in combination with lipopolysaccharide (LPS) and live BCG vaccine. Deodan was applied at a dose of 150 mg/kg and various treatment schedules were employed. The serum levels of TNF alpha in treated mice were quantified by ELISA. Oral administration of Deodan at a dose of 150 mg/kg for 1, 3, 10 or 20 consecutive days only enhanced serum TNF alpha levels in treated mice. Maximal TNF alpha levels were reached 6 h after the last application of Deodan. Deodan was effective in priming TNF alpha in mice triggered intravenously (i.v.) with LPS. Deodan triggered the production of TNF alpha in BCG-primed mice. The preparation, however, was not an effective trigger of mice primed intradermally (i.d.) with 1 microgram/mouse LPS. These findings suggest that Deodan is both a primer and trigger of endogenous TNF alpha. The advantages of treatment of neoplastic disease with agents which induce endogenous TNF alpha is discussed.
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PMID:Endogenous production of tumor necrosis factor in normal mice orally treated with Deodan--a preparation from Lactobacillus bulgaricus "LB51". 146 68

Assessment of cell-mediated immunity (CMI) is an integral part of preclinical studies of pharmaceuticals and xenobiotics. Even if several tests to determine CMI are available, their interpretation is fraught with uncertainty whether identical results can be expected for each of these particular tests after the challenge with different immunomodulatory substances. This dilemma has been addressed by investigating the changes in two basic tests of CMI in vivo, i.e. delayed-type hypersensitivity (DTH) to sheep red blood cells and regional graft-versus-host reaction (GVHR), after the challenge with several immunomodulators. Both immunosuppressive modifiers (monoclonal anti-Thy 1, 2 antibody, cyclophosphamide, dexamethasone, methotrexate) and immunostimulatory agents (lipopolysaccharide, double-stranded RNA, thymostimulin, adamantylamide dipeptide, Propionibacterium parvum, BCG), were used. Most of the immunosuppressive drugs stimulated DTH while inhibiting GVHR. Most of the immunostimulating substances suppressed DTH and failed to affect GVHR. The results of tests were time dependent. Regional GVHR and DTH cannot be used as mutually interchangeable in immunomodulatory testing, and different results of these tests after exposure to a given agent can be expected. Possible mechanisms of action which would explain these differences are suggested in the discussion.
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PMID:Validity of delayed-type hypersensitivity and graft-versus-host reaction in testing of immunomodulators. 159 52

We examined the potential of two bacterial immunomodulators, trehalose dimycolate (TDM) and lipopolysaccharide (LPS), to stimulate the capacity of mouse peritoneal macrophages to control the growth of the intracellular bacterium, Mycobacterium tuberculosis BCG. Macrophages were obtained from mice innately susceptible (Bcgs) or resistant (Bcgr) to BCG infection. In all mouse strains tested (Bcgr and Bcgs), with the exception of BALB/c (Bcgs), TDM was sufficient to elicit macrophages with strong antimycobacterial activity in vitro. In BALB/c mice, the induction of anti-BCG activity required two signals, TDM and LPS, given in sequence. Our data suggest that additional gene(s), besides the Bcg locus, control macrophage resistance to BCG.
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PMID:Stimulation of antimycobacterial activity in mouse peritoneal macrophages by priming with trehalose dimycolate (TDM). 179 48

The biological stains, methylene blue and its metabolite azure B, were evaluated as anti-tumor and anti-inflammatory agents. Azur B, administered in drinking water to tumor-bearing mice, inhibited the growth of transplanted tumors and the growth of primary tumors induced by methylcholanthrene. Inhibition of growth of primary tumors was observed only in female mice. Azure B also reduced the wet weight of carrageenin-induced granulomas in rats. Azure B, given intravenously to BCG-sensitized mice 15 minutes prior to challenge with lipopolysaccharide, decreased TNF production (to 10% of control values) and prevented death from endotoxic shock. Methylene blue decreased TNF production (to 50% of control values) but did not protect the animals from endotoxic shock. Our results suggest that some of the effects previously ascribed to methylene blue are probably mediated via its metabolite, i.e. azure B. Low toxicity and easy administration of the dyes explain their use in clinical settings.
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PMID:Anti-tumoral and anti-inflammatory effects of biological stains. 181 Jan 51

To elucidate the mechanism of tumor necrosis factor (TNF) production, we analyzed proteins produced in macrophages sharing the epitope of TNF according to the priming and triggering of TNF production. Rabbit alveolar macrophages primed with Bacillus Calmette-Guerin (BCG) were isolated and cultured in vitro with 35S-methionine, and the proteins produced were analyzed using anti-rabbit TNF monoclonal antibody. Primed with BCG, alveolar macrophages synthesized two proteins with molecular sizes of 50 and 17 kilodaltons (kDa) (p50 and p17) sharing the same epitope with mature TNF within the cells. These two proteins were released into the medium where other proteins were detected without TNF-activity. Cultured with lipopolysaccharide (LPS triggering), the primed alveolar macrophages released TNF-activity into the medium where p17 together with many larger proteins was detected by immunoprecipitation. In vitro translation of messenger ribonucleic acid (mRNA) from BCG-primed macrophages showed that primary TNF has a molecular size of 28 kDa (p28). These results suggest that active TNF of p17 is secreted when triggered via post-translational processing of the precursor molecules synthesized through priming with BCG.
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PMID:Post-translational processing of tumor necrosis factor production. 205 66

The roles of secreted and membrane-associated TNFs were investigated in activated macrophage cytolysis of L929, EMT-6, and P815 targets. While all three targets were susceptible to cytolysis in coculture, an anti-TNF antiserum blocked lysis of L929 and EMT-6 but not of the P815 targets. Of the three targets, recombinant human or mouse TNF could only lyse the L929 target; despite the fact that a role for TNF was invoked in lysis of EMT-6 targets in coculture, the latter was strongly resistant to soluble rTNF, even at concentrations 30-40-fold higher than the Ka for its TNF-receptor. Cytolysis of the L929 target occurred when it was cocultured with BCG-activated macrophages even when these effector cells did not secrete TNF, either due to prior chemical crosslinking or to lack of exposure to a triggering level of lipopolysaccharide. Furthermore, by introduction of the anti-TNF antiserum over a dose-range, it was shown that macrophage cytolysis both of L929 and EMT-6 targets occurred in the absence of bioavailable, fluid-phase TNF. Thus, even for targets susceptible to fluid-phase TNF, TNF-dependent, direct macrophage-mediated cytolysis appears to be a function independent of secreted TNF and one that utilizes effector-target contact to express the action of a membrane form of the molecule.
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PMID:Tumoricidal effector mechanisms of murine BCG-activated macrophages: role of TNF in conjugation-dependent and conjugation-independent pathways. 216 18

We studied the production of tumor necrosis factor alpha (TNF-alpha) by peripheral blood monocytes taken from patients with pulmonary tuberculosis and from healthy controls. It was found that the monocytes from patients with newly diagnosed tuberculosis released significantly greater amounts of TNF-alpha in vitro in response to lipopolysaccharide than did those from healthy controls (P less than 0.05). However, the monocytes from patients with chronic refractory tuberculosis released significantly lower amounts of TNF-alpha than did those from patients with newly diagnosed tuberculosis (P less than 0.005). Even when the cells were primed for 24 h with 500 U of recombinant interferon gamma per ml, the same pattern of results was observed. The depressed TNF-alpha production by the monocytes from patients with chronic refractory tuberculosis was also shown in response to Mycobacterium bovis BCG. This depressed TNF-alpha production did not recover, even when cultured for 1 to 7 days in the sera of healthy individuals. The sera from patients with chronic refractory tuberculosis did not have any suppressive effect on the lipopolysaccharide-induced TNF-alpha production. Thus, it was demonstrated that the levels of TNF-alpha produced by monocytes were related to the disease states of pulmonary tuberculosis and that the depressed TNF-alpha production by monocytes in patients with chronic refractory tuberculosis might not be acquired.
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PMID:Production of tumor necrosis factor alpha by monocytes from patients with pulmonary tuberculosis. 220 76

Quartz but not titanium dioxide (TiO2) induced the production of reactive oxygen metabolites (ROM) by human monocyte-derived macrophages, as measured by lucigenin dependent chemiluminescence. Activation of the macrophages with BCG, bacterial lipopolysaccharide and macrophage-activating factor (MAF) caused a prominent increase of quartz-induced ROM production, MAF having the strongest effect. The activation did not affect the TiO2 responses to the same extent. Assuming that ROM have a role in the pathogenesis of silica-induced disease in man, we suggest that enhancement of quartz-induced production of ROM by activated pulmonary macrophages may at least partly explain the experimental and epidemiological data indicating that activation of the immune system during infection promotes the development of silicosis.
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PMID:Quartz-induced production of reactive oxygen metabolites by activated human monocyte-derived macrophages. 222 36


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