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 mitogens concanavalin A (Con A) and bacterial lipopolysaccharide (LPS) stimulated normal spleen cells of DBA/2J, CBA/J, and BALB/c mice about equally in the presence of either isologous or homologous serum. This system revealed that sera from mice with five different methylcholanthrene-induced rhabdomyosarcomas inhibited mitogen stimulation of normal spleen cells. Sera from mice with a mammaryadenocarcinoma and spontaneous rhabdomyosarcoma were similarly suppressive. In contrast, sera from mice with melanoma were not inhibitory and often enhanced stimulation. Sera from tumor-bearing animals had the same effects both qualitatively and quantitatively on cells from the strain carrying the tumor and on cells from the other two strains. The mixed lymphocyte response of CBA/J times BALB/c spleen cells was affected exactly as were the responses to mitogen by the various sera. Stimulation by mitogen of mouse lymph-node cells and spleen cells with macrophages removed, as well as that of guinea pig spleen cells, was also inhibited by sera from mice with rhabdomyosarcoma and mammary adenocarcinoma.
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PMID:Effects of sera from tumor-bearing mice on mitogen and allogeneic cell stimulation of normal lymphoid cells. 12 99

Neonatal female NMRI mice were given injections of olive oil (controls) or daily doses of corticosterone (10 micrograms), 17 beta-estradiol (10 micrograms), or diethylstilbestrol (DES) (0.01, 0.1, 1, or 5 micrograms) for the first 5 days after birth. The 5-micrograms dose of DES resulted in a persistently reduced in vitro mitogen response to concanavalin A or bacterial lipopolysaccharide of spleen lymphocytes from 6-, 10-, and 18-week-old or 17-month-old females. DES injections from day 6 through day 10 did not influence the later mitogen response. Treatment of ovariectomized 10-week-old females with 5 micrograms DES for 5 days resulted in a tendency to a reduced mitogen response (not statistically significant) 24 hours after the last DES injection. Four weeks later, the mitogen response was the same in experimental and control females. Different possible mechanisms for the persistent effect on the mitogen response are discussed. Neonatal DES treatment not only resulted in persistent changes in the cervicovaginal epithelium and in the hypothalamic-pituitary gland control system but also in the spleen lymphocyte mitogen response. The altered mitogen response should be a stimulus for a detailed analysis of the immune system in women exposed to DES during fetal life, some of whom develop later in life clear cell adenocarcinoma of the uterine cervix and vagina.
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PMID:Long-term effects of neonatal estrogen treatment on mitogen responsiveness of mouse spleen lymphocytes. 28 31

Most biliary tract cancers are advanced and inoperable when first diagnosed. Even if surgery can be performed, the postsurgical prognosis of these diseases is poor. In the present study, we investigated effective chemotherapies for a human bile duct cancer xenograft cell line (undifferentiated carcinoma, BDC-SN) and a gall bladder cancer xenograft cell line (well-differentiated adenocarcinoma, GBC-GN), which were transplanted into nude mice. Eight anticancer agents (CDDP, 5-FU, VDS, MMC, ADR, EPIR, CQ, and VP-16) and their various combinations were evaluated at 2-4 times the clinical dose. When used singly, CDDP, 5-FU, and VDS were effective against BDC-SN, and only CDDP was effective against GBC-GN. Among the various 2-agent combinations, CDDP + 5-FU was the most effective against both BDC-SN and GBC-GN. However, 3-agent combinations consisting of CDDP + 5-FU + another agent were less effective than the CDDP + 5-FU double regimen and caused significant loss of weight as well as high mortality. These results suggest that CDDP + 5-FU may be the most useful regimen against biliary tract cancers in clinical application.
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PMID:Experimental chemotherapy for xenograft cell lines of human bile duct and gall bladder cancers in nude mice. 143 61

Leukocyte-endothelium interaction in vivo consists of the rolling of leukocytes along the vascular wall and, under certain conditions, their adherence to endothelial cells. In a rat tumor microcirculation model (mammary adenocarcinoma implanted in rat skinfold window chamber), we demonstrated that this interaction, measured as flux of rolling leukocytes and density of adhering leukocytes, was significantly reduced in tumor microvessels compared to normal microvessels, both under control conditions and during inflammation induced by N-formylmethionylleucylphenylalanine (1 microM), bacterial lipopolysaccharide (1 microgram/ml), or tumor necrosis factor alpha (500 units/ml). We also measured the blood flow shear rate in the tumor and normal microvessels and found that the difference in shear rate between the two types of microvessels could not account for the differences in leukocyte-endothelium interaction. The diminished leukocyte-endothelium interaction in tumors under various stimulated conditions suggests that a number of adhesion molecules may not be expressed properly on tumor endothelial cells.
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PMID:Diminished leukocyte-endothelium interaction in tumor microvessels. 163 39

The liver macrophage population was fractionated according to cell size into three subpopulations by means of elutriation centrifugation. The total liver macrophage population and the three subpopulations were cultured and exposed to the immunomodulators muramyl dipeptide (MDP), in a free or liposome-encapsulated form, and/or lipopolysaccharide (LPS). The tumor cytotoxic activity thus induced in the populations, the preservation of this activity and the response to a second stimulus were studied. The in vitro induced cytolytic activity was determined by a radioactivity release assay, using C26 colon adenocarcinoma cells, labeled with [methyl-3H]thymidine, as target cells. MDP or LPS readily activated the total macrophage population in maintenance culture to a tumor cytotoxic state during the first 2 days after isolation. Four days after isolation, the activation induced with both MDP and LPS was strongly reduced. The small to intermediate-size macrophages could be activated to tumor cytotoxic activity with MDP for up to 3 days and with LPS for up to 4 days in culture. The large-size macrophages could only be activated up to day 2 in culture with MDP or LPS or both. The combination of MDP and LPS, however, induced all cell populations in a synergistic way to become cytolytic for up to 4 days in culture. With free MDP as an activator, the activated state decayed within 1 day to almost zero levels, but less rapidly in the small cells than in the large cells. With liposome-encapsulated MDP, the activated state was preserved considerably longer, except in the largest cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maintenance of tumoricidal activity and susceptibility to reactivation of subpopulations of rat liver macrophages. 186 44

Conditioned medium (CM) from cultures of cytotoxic activated macrophages causes inhibition of mitochondrial respiration, DNA synthesis, and aconitase activity in murine EMT-6 mammary adenocarcinoma cells by an L-arginine dependent effector mechanism. CM induces cytotoxicity and nitrite synthesis in EMT-6 cells in a dose dependent manner. We have identified the soluble factors in CM that induce cytotoxicity and synthesis of inorganic nitrogen oxides from L-arginine by EMT-6 cells. Using functional inhibition experiments, the activity of lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma) in CM was investigated. The LPS inhibitor polymyxin B and TNF alpha antibody produced a modest decrease in nitrite production, while IFN gamma antibody markedly inhibited both nitrite production and cytostasis. Simultaneous treatment with polymyxin B, TNF alpha antibody, and IFN gamma antibody reduced EMT-6 cell nitrite production by 81%, and cytostasis by 74%. By Western blot, IFN gamma and TNF alpha were shown to be present in CM. When CM was subjected to hydrophobic interaction chromatography, a single peak of activity was eluted, and Western blot showed that the active fractions contained IFN gamma. Furthermore, IFN gamma antibody neutralized the activity in these chromatographic fractions. We conclude that induction of inorganic nitrogen oxide synthesis from L-arginine by the synergistic combination of IFN gamma, TNF alpha, and LPS accounts for most of the biologic activity of CM, and that IFN gamma is the major priming factor.
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PMID:Activated macrophage conditioned medium: identification of the soluble factors inducing cytotoxicity and the L-arginine dependent effector mechanism. 190 65

The murine adenocarcinoma cell line TA 3 synthesized nitrite from L-arginine upon stimulation with gamma-interferon (IFN-gamma) associated with tumor necrosis factor (TNF), and/or bacterial lipopolysaccharide (LPS), but not with IFN-gamma, TNF, or LPS added separately. Induction of the NO2(-)-generating activity caused an inhibition of DNA synthesis in TA 3 cells. This inhibition was prevented by the L-arginine analog N omega-nitro-L-arginine, which inhibited under the same conditions nitrite production by TA 3 cells. The TA 3 M2 subclone, selected for enhanced ribonucleotide reductase activity, was found to be less sensitive than the wild phenotype TA 3 WT to the cytostatic activity mediated by the NO2(-)-generating system. Cytosolic preparations from TA 3 M2 cells treated for 24 or 48 h with IFN-gamma, TNF, and LPS exhibited a reduced ribonucleotide reductase activity, compared to untreated control cells. No reduction in ribonucleotide reductase activity was observed when N omega-nitro-L-arginine was added to treated cells. Addition of L-arginine, NADPH, and tetrahydrobiopterin into cytosolic extracts from 24-h treated TA 3 M2 cells triggered the synthesis of metabolic products from the NO2(-)-generating pathway. This resulted in a dramatic inhibition of the residual ribonucleotide reductase activity present in the extracts. The inhibition was reversed by NG-monomethyl-L-arginine, another specific inhibitor of the NO2(-)-generating activity. No L-arginine-dependent inhibition of ribonucleotide reductase activity was observed using extracts from untreated cells that did not express NO2(-)-generating activity. These results demonstrate that, in an acellular preparation, molecules derived from the NO2(-)-generating pathway exert an inhibitory effect on the ribonucleotide reductase enzyme. This negative action might explain the inhibition of DNA synthesis induced in adenocarcinoma cells by the NO2(-)-generating pathway.
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PMID:Alterations of ribonucleotide reductase activity following induction of the nitrite-generating pathway in adenocarcinoma cells. 211 5

Activated macrophages mediate cytotoxicity against tumor targets and thus may modulate development and growth of metastatic tumor cells. Macrophage colony stimulating factor (M-CSF) has a potential role in activating mature macrophages to a cytotoxic state. We employed a murine Kupffer cell (KC) model of cytotoxicity against a tumor necrosis factor (TNF) - sensitive murine colon adenocarcinoma cell line (MCA26) to evaluate the ability of recombinant human M-CSF (rhM-CSF) 1) to act alone as a KC-activating agent and 2) to enhance KC cytotoxicity against MCA26 cells in association with known macrophage activating compounds. rhM-CSF produced a dose-dependent increase in TNF release by KC in vitro with a parallel increase in MCA26 killing. KC activated by rhM-CSF produced less TNF and concomitantly demonstrated a lower cytotoxicity against MCA26 cells when compared with KC activated by gamma interferon (gamma IFN) with or without lipopolysaccharide (LPS). M-CSF did not act in a synergistic fashion with gamma IFN and LPS to increase TNF secretion or cytotoxicity against MCA26 cells. rhM-CSF thus acts as a single agent capable of activating murine KC to a cytotoxic state but does not cooperate with classical priming/triggering signals to achieve KC activation.
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PMID:Human recombinant macrophage colony stimulating factor activates murine Kupffer cells to a cytotoxic state. 211 71

Treatment of EMT 6 mammary adenocarcinoma cells with Interferon-gamma (IFN-gamma, 10 U.ml-1) plus endotoxin lipopolysaccharide (LPS, 100 ng.ml-1) induces concomitantly a growth arrest and production of citrulline and nitrite from L-arginine. A similar L-arginine-dependent metabolism is responsible for the vascular smooth muscle relaxing effect of stimulated endothelial cells. We therefore investigated the ability of EMT 6 cells to induce the relaxation of endothelium-denuded rat aortic rings precontracted with noradrenaline (1 microM). Pretreatment of EMT 6 cells with IFN-gamma + LPS increased their relaxing potency by 5-10 times. The relaxin effects of control and treated EMT 6 cells were entirely counteracted by NG-monomethyl-L-arginine (300 microM), a specific inhibitor of nitrite and citrulline production from L-arginine, and by methylene blue (10 microM) and LY 83583 (10 microM), two inhibitors of NOo-induced activation of guanylate cyclase. The effect of NG-monomethyl-L-arginine was reversed by L- but not D-arginine (1 mM). It is concluded that IFN-gamma + LPS increase the production of a relaxing factor in EMT 6 cells through the L-arginine-NOo-synthase pathway.
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PMID:Production of an arginine-derived relaxing factor induced by IFN-gamma plus endotoxin in murine adenocarcinoma EMT 6 cells. 212 6

Using an immunogenic nonmetastatic murine mammary adenocarcinoma (D1-DMBA-3) induced in BALB/c mice by dimethylbenzanthracene, we have previously shown that splenocytes from tumor bearers have depressed lymphocyte responses to mitogens and antigens, including tumor-associated antigens. In addition, they display decreased natural killer and T-cell cytotoxic activities. Macrophages from tumor-bearing mice appear to be responsible for the suppression of T- and B-cell responses to concanavalin A, lipopolysaccharide, and tumor-associated antigens observed in tumor bearers. The appearance of these macrophages in the spleen tightly parallels the progressive growth of the tumor and the concomitant immunosuppression. Simultaneously high levels of macrophage progenitors were observed in blood, bone marrow, lung, and liver. A significant increase of colony-stimulating activity of the granulocyte-macrophage lineage was detected in the sera from tumor-bearing mice. Higher levels of this colony-stimulating activity (CSA) were detected in tumor cystic fluid as compared with the levels in serum. A tumor cell line established in vitro from the D1-DMBA-3 in vivo tumor produces high levels of a factor with CSA in culture supernatant fluids. Partial purification of the CSA from the tumor cell line supernatants was achieved using CentriCell ultrafiltration and SephacrylS-300 chromatography. These studies revealed that the molecular weight of the colony-stimulating-like factor is 32,000 to 35,000. The morphology of the colonies obtained in cultures using this factor is similar to that of the colonies that develop in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) but not with macrophage colony-stimulating factor (M-CSF). CSA from tumor cell supernatants was neutralized by antiserum to GM-CSF but not with anti-M-CSF or anti-granulocyte colony-stimulating factor (G-CSF). Macrophages from bone marrow or peritoneal exudates from normal mice cultured with tumor supernatant for 2 to 3 days strongly inhibit normal splenocyte responses to concanavalin A and lipopolysaccharide. The data suggest that the tumor releases a GM-CSF that alters the hemopoietic system and induces or expands macrophages, which exert a suppressive function on the immune system of tumor-bearing mice.
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PMID:Expansion of immunoregulatory macrophages by granulocyte-macrophage colony-stimulating factor derived from a murine mammary tumor. 213 4


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