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)

We previously demonstrated that macrophages isolated from human malignant effusions support colony formation of autologous tumor cells in soft agar. We now demonstrate that macrophages (derived from effusions of patients with ovarian, breast, colon, or lung adenocarcinomas) secrete a soluble factor(s) that enhances the ability of a human epithelial tumor cell line (SW-13) to clone in soft agar. Macrophages increased colony growth 5 to 10-fold in a concentration dependent manner, although inhibition of cell growth was observed in the presence of high concentrations of macrophages. We attempted to increase production of tumor colony stimulating factor by exposing macrophages to lipopolysaccharide, concanavalin A, or phytohemagglutinin. Exposure of macrophages to these agents failed to increase their ability to secrete stimulatory factors. Macrophages were cultured for 1 day to 6 weeks in the presence of GCT-CM, a source of granulocyte-macrophage colony stimulating factor and the ability of these cultured macrophages to support colony growth assessed. The ability of macrophages to support colony growth declined gradually with time in culture reaching 50% of control values at 14 days, but remained at this level until 5 weeks of culture. The results of this study indicate the SW-13 cells may provide a quantitative assay for studying monocyte-derived tumor colony stimulating factors.
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PMID:Growth factors for human tumor clonogenic cells elaborated by macrophages isolated from human malignant effusions. 348 26

We describe the biologic characteristics of an activity produced by human monocyte-derived lipid-containing cells (MDLCCs) that enhances the colony-forming capacity of granulocyte-macrophage progenitors (CFU-GM). Medium conditioned by well-developed MDLCCs (at day 21 to day 28 of cultivation) was added to bone marrow cultures containing GCT cell line-conditioned medium (GCT-CM) or other material as a source of granulocyte-macrophage colony-stimulating factors (GM-CSFs). MDLCC-conditioned medium (CM) had no detectable granulocyte-macrophage colony-stimulating activity (GM-CSA), but it contained an activity that enhanced the colony number in both day 7 and day 14 CFU-GM cultures. Dose-response curves for GCT-CM in the presence of MDLCC-CM demonstrated that this enhancing effect occurred at concentrations of GM-CSFs that stimulate maximal CFU-GM growth. This enhancing effect was seen with both granulocytic and monocytic progenitor cells. It was titratible and required the continuous presence of MDLCC-CM from initiation of culture. No enhancement was noted when MDLCC-CM was added 48 hours after plating. The enhancement still occurred when marrow cells were first incubated with MDLCC-CM and GCT-CM was added at later times. Neither the enhancing activity nor its production was dependent on horse serum contained in MDLCC culture medium. The enhancing effect was also seen when other sources of GM-CSA were used: medium conditioned by 5637 cell line, phytohemagglutinin-stimulated lymphocytes (PHAL), or placenta tissue. Furthermore, this enhancing activity appeared to be specific for CFU-GM. Addition of MDLCC-CM to mixed and erythroid cultures, stimulated by suboptimal and optimal concentrations of PHAL-CM did not modify the number of mixed colonies or erythroid bursts. This granulomonopoietic enhancing activity contained in MDLCC-CM was heat stable (56 degrees C and 75 degrees C for 30 minutes) and nondialyzable (3,500 and 14,000 molecular weight cut off tubing). Its production was increased by treating MDLCC with lipopolysaccharide (5 micrograms/mL) or zymosan (60 micrograms/mL) and inhibited by lactoferrin (10(-7) mol/L). The production of a granulomonopoietic enhancing activity by MDLCCs represents the demonstration of another positive feedback regulator of myelopoiesis involving the monocyte-macrophage system.
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PMID:Biological characterization of a granulomonopoietic enhancing activity derived from cultured human lipid-containing macrophages. 387 61

Recent clinical studies using neutralizing antibodies point to a key role for tumor necrosis factor-alpha (TNF-alpha) in chronic inflammatory diseases. Antisense technique is a recent approach aiming at inhibition of single proteins. Previously, we described nonspecific induction of TNF by phosphorothioate oligonucleotides. In this study, we established an in vitro model that allows specific inhibition of TNF synthesis, bypassing TNF induction. Freshly isolated human monocytes were incubated with oligonucleotides and the cationic lipid lipofectin in different ratios. TNF synthesis was stimulated with lipopolysaccharide and quantified by a specific radioimmunoassay (RIA). Among all sequences tested, one of the antisense oligonucleotides complementary to the translation initiation region of TNF mRNA (5'-CAT GCT TTC AGT CAT-3') revealed highest efficacy. At 2 microM, the antisense oligonucleotide inhibited TNF synthesis by up to 79%. A concentration as low as 250 nM of the antisense oligonucleotide was effective. Scrambled controls and controls with different, defined degrees of mismatches confirmed a sequence-specific action. Examination with confocal fluorescence microscopy showed a marked difference comparing lipofectin-mediated vs. spontaneous uptake. This study defines criteria that from the prerequisite necessary for design and application of antisense oligonucleotides against TNF in vivo.
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PMID:Specific suppression of human tumor necrosis factor-alpha synthesis by antisense oligodeoxynucleotides. 901 65