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)

The 52 kD myeloid membrane glycoprotein CD14 represents the receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP); it is involved in LPS induced tumor necrosis factor-alpha production. Expression of CD14 increases in monocytes differentiating into macrophages, and it is reduced by rIFNg in monocytes in vitro. In the present study CD14 membrane antigen expression was investigated in cultures of human mononuclear leucocytes (PBL), in elutriated, purified monocytes, and in blood monocyte derived Teflon cultured macrophages. Cells were incubated for 15 or 45 h with rIL-1, rIL-2, rIL-3, rIL-5, rIL-6, rTNFa, rGM-CSF, rM-CSF, rTGFb1, rIFNa, lipopolysaccharide (LPS), and, as a control, rIFNg. The monoclonal antibodies Leu-M3 and MEM 18 were used for labelling of CD14 antigen by indirect immunofluorescence and FACS analysis of scatter gated monocytes or macrophages. IFNg concentrations were determined in PBL culture supernatants by ELISA. rIFNa and rIL-2 reduced CD14 in 15 and 45 h PBL cultures, an effect mediated by endogenous IFNg, since it was abolished by simultaneous addition of an anti-IFNg antibody. rIFNa and rIL-2 were ineffective in purified monocytes or macrophages. rIL-4 strongly reduced CD14 in PBL and purified monocytes after 45 h, whereas in macrophages the decrease was weak, although measurable after 15 h. The other cytokines investigated did not change CD14 antigen expression. Cycloheximide alone reduced CD14, but when added in combination with rIFNg the effect on CD14 downregulation was more pronounced. The effect of rIFNg on CD14 in PBL cultures was dose-dependently inhibited by rIL-4 and this inhibition is probably due to an IL-4 mediated blockade of IFNg secretion. LPS at a low dose increased CD14, at a high dose it produced a variable decrease of CD14 in PBL, which was probably due to LPS induced IFNg secretion. LPS strongly enhanced CD14 in 45 h cultures of purified monocytes. The results, showing that CD14 antigen expression is upregulated by LPS and downregulated by rIFNg and rIL-4, suggest that the LPS-LBP receptor is involved in the feedback response of IFNg and IL-4 to LPS stimulation.
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PMID:Effect of cytokines and lipopolysaccharide on CD14 antigen expression in human monocytes and macrophages. 172 47

Phagocytosis of Giardia lamblia trophozoites by cytokine-activated and non-activated bone marrow-derived macrophages was examined in vitro. Macrophages treated with recombinant interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) ingested a significantly higher number of in vitro-grown trophozoites than untreated macrophages. Maximal uptake of parasites occurred after 4 h and 6 h of incubation where 81.4% and 79.1% of macrophages were positive for trophozoites. Other cytokines tested, IL-2, IL-3, IL-4, IL-5, GM-CSF, CSF-1 and tumour necrosis factor-alpha (TNF-alpha) either alone or in combination with LPS, failed to activate macrophages to phagocytose G. lamblia. The induction of this activated macrophage anti-microbial function was achieved pharmacologically using phorbol myristate acetate (PMA) and ionophore A23187. The giardicidal activity of macrophages activated with IFN-gamma and LPS or that induced by PMA and A23187 was inhibited by H-7, indicating the role for protein kinase C in the intracellular events following activation.
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PMID:Phagocytosis of Giardia lamblia trophozoites by cytokine-activated macrophages. 173 94

Abnormal parturition can be followed by a persistent endometritis which can have deleterious effects on the cow's subsequent reproductive performance. Normal and active uterine defense mechanisms have been reported to be very important for the exclusion of bacterial infection from the uterus and recovery from endometritis developing after parturition. Despite the widespread use of local or systemic antibiotics, antiseptics, sulfonamides and hormones, rates of recovery from endometritis and the cow's subsequent fertility have not increased appreciably. Furthermore, the cost of any treatment, the frequency of its administration and the milk disposal after treatment make their use uneconomic. Alternative therapies which stimulate the natural uterine defense mechanisms have been suggested as treatments of bovine endometritis. These include: (I) Endotoxins such as lipopolysaccharide of E. coli, (II) serum, plasma or hyperimmune serum, (III) polymorphonuclear leucocyte (PMN) extracts and components and (IV) granulocyte-macrophage colony stimulating factors (G-M CSF).
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PMID:Bovine endometritis: current and future alternative therapy. 177 86

Treatment of fresh non-adherent bone marrow cells (NABMC) with cisplatin or lipopolysaccharide (LPS) did not render them tumoricidal. NABMC incubated in medium alone or medium containing recombinant granulocyte macrophage colony stimulating factor (rGM-CSF) for 4 days matured to macrophages that were positive for non-specific esterase staining. Bone marrow-derived macrophages cultured with medium alone did not respond to cisplatin or LPS by the induction of tumoricidal activity, whereas rGM-CSF derived bone macrophages showed significantly enhanced cytotoxicity after treatment with cisplatin or LPS. Culturing of NABMC with rGM-CSF enhanced cell survival compared to the cells incubated in medium alone. These results suggest that bone marrow cells not only mature in rGM-CSF, but are also primed by rGM-CSF for induction of tumoricidal activity.
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PMID:In vitro activation of rGM-CSF derived bone marrow macrophages by cisplatin and lipopolysaccharide. 178 94

Colony-stimulating factor 1 (CSF-1) can act on mature macrophages to modulate their production of inflammatory cytokines. A cDNA encoding the interleukin-1 receptor antagonist (IL-1Ra) was cloned by subtractive hybridization from a CSF-1-stimulated murine macrophage cell line, sequenced, and expressed in mammalian and bacterial cells. Mouse IL-1Ra is a 22-Kd glycoprotein that is 76% identical to its human counterpart, shows considerably less similarity to IL-1 alpha and IL-1 beta, and competes with IL-1 alpha for binding to the type I IL-1 receptor normally expressed on T cells and fibroblasts. CSF-1 treatment of mouse bone marrow-derived macrophages led to a rapid and sustained increase in IL-1Ra mRNA during the G1 phase of the cell cycle as well as to increases in mRNAs encoding IL-1 alpha and IL-1 beta. Cycloheximide inhibited CSF-1-induced IL-1 alpha mRNA synthesis, but augmented IL-1 beta mRNA production and did not affect induction of IL-1Ra mRNA. No IL-1Ra mRNA was observed in CSF-1-stimulated mouse fibroblasts engineered to express CSF-1 receptors, demonstrating that its regulation depends on cell context and can be dissociated from the proliferative response. In agreement, bacterial lipopolysaccharide, a nonmitogenic activator, also induced IL-1Ra and IL-1 mRNAs in macrophages. Unlike IL-1 alpha and beta, IL-1Ra contains a signal peptide. The kinetics of its induction and its ability to gain access to the secretory compartment imply that IL-1Ra may be secreted more efficiently than IL-1, and suggest that macrophages both positively and negatively regulate the IL-1 response.
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PMID:Cloning and expression of murine interleukin-1 receptor antagonist in macrophages stimulated by colony-stimulating factor 1. 183 Apr 98

We have shown that certain murine tumors grow more slowly and spread less readily in immune deficient animals. We have also demonstrated that immunologic factors explain certain aspects of this difference. In the work presented we demonstrate that a subpopulation of splenocytes produce a factor(s) that enhances tumor cell proliferation in vitro. We also describe an in vitro model to determine the level of tumor stimulatory activity. We found that the tumor cell growth-enhancing activity (TEA) is heat stable but sensitive to trypsin digestion, low pH and beta-mercaptoethanol. TEA production is found to be insensitive to mitogen stimulation such as concanavalin A, lipopolysaccharide, and phytohemagglutinin. Among the known growth factors and interleukins we have tested (interleukin 1-7, basic FGF, EGF, TGF-beta PDGF, GM-CSF, and MCSF), none appear to account for TEA activity.
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PMID:Initial description of a tumor enhancing activity produced by murine splenocytes. 188 89

The effects of GM-CSF, IL-2, IFN-gamma, TNF-alpha and IL-6 on the production of IL-1 (both secreted and cell associated) and TNF-alpha by peripheral blood monocytes were studied. Monocytes were cultured for 20 h in suspension and in serum-free conditions which minimized background stimulation of monokine production. GM-CSF, IL-2 and TNF-alpha directly induced the production of cell-associated IL-1 but little or no IL-1 or TNF-alpha secretion. Combination of GM-CSF with IFN-gamma, IL-2 or TNF-alpha synergistically enhanced IL-1 secretion and had an additive effect on cell-associated IL-1 production. Combination of IL-2 with IFN-gamma or TNF-alpha also synergistically enhanced IL-1 secretion but the effect on cell-associated IL-1 production was less than additive. GM-CSF synergistically enhanced TNF-alpha secretion induced by IFN-gamma but not by lipopolysaccharide. GM-CSF did not enhance TNF-alpha secretion induced by IL-2 or TNF-alpha. In contrast, IL-2 synergistically enhanced TNF-alpha secretion induced by IFN-gamma. These results are discussed in relation to cytokine involvement in rheumatoid arthritis.
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PMID:Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-6 on the production of immunoreactive IL-1 and TNF-alpha by human monocytes. 190 83

Twenty-four Haemophilus influenzae type b strains from 836 children and young adults in an open population were subtyped by outer-membrane-protein (OMP) analysis on sodium dodecyl sulphate-polyacrylamide gels, lipopolysaccharide serotyping and biotyping. The results were compared with those obtained with H. influenzae type b strains from 97 patients with meningitis in the same city (Amsterdam). OMP subtype 1 was significantly more common among the CSF isolates than in carrier strains (82% vs 50%; p less than 0.002). The other OMP subtypes found among carriers were rarely isolated from patients. The lipopolysaccharide serotype and biotype distribution did not differ between the two groups. The combination of OMP subtype 1, lipopolysaccharide 1, biotype I was much more common in isolates from patients than in those from carriers (71% vs 42%; p less than 0.01). The data suggest that various H. influenzae type b subtypes are less virulent than those commonly isolated from invasive infections.
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PMID:Differences in subtype distribution of Haemophilus influenzae type b from carriers in the general population and patients with meningitis. 205 15

Colony stimulating factor (CSF)-rich serum was obtained from mice injected intraperitoneally (ip) with shosaiko-to, a traditional Chinese herbal medicine. Transfer of the CSF-rich serum into naive mice augmented the resistance against Listeria monocytogenes. A dose-dependent induction of CSF was observed in mice given shosaiko-to via intravenous route as well as via intraperitoneal route. Since the serum CSF induction was observed in both lipopolysaccharide (LPS)-responder C3H/He mice and LPS-non-responder C3H/HeJ mice, the effect of shosaiko-to seemed to be independent of possibly contaminating LPS. The level of serum CSF induced by shosaiko-to in athymic nude mice was similar to that in control euthymic mice, and the induction of CSF was completely blocked by the previous administration of carrageenan, a selective macrophage-blocker. In mice treated ip with shosaiko-to CSF activity was detected in the peritoneal cavity, the site of injection, and the time course was similar to that of serum CSF induction. In a bone marrow culture system, the composition of colonies formed by shosaiko-to-induced CSF was similar to that formed by standard GM-CSF. The CSF activity was scarcely affected by treatment of the sera with anti-M-CSF antibody. These results suggest that shosaiko-to augments the host defense by inducing mainly GM-CSF, and that CSF is produced by cells of macrophage lineage. In addition, it was shown that CSF could be induced even after oral administration of herbal medicines.
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PMID:Induction of colony-stimulating factor(s) after administration of a traditional Chinese medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to). 209 44

We investigated the capacity of mouse bone marrow-derived macrophages (BMDM) to produce interleukin 1 (IL 1), interleukin-6 (IL 6), and tumor necrosis factor (TNF) upon lipopolysaccharide (LPS) stimulation. BMDM were allowed to differentiate either in the presence of conditioned medium (from WEHI-3 or L cells), or in the presence of recombinant cytokines (IL 3, macrophage-colony stimulating factor [M-CSF], or granulocyte/macrophage-colony stimulating factor [GM-CSF]). Cells were maintained in culture up to 3 weeks and tested at different times. Significant spontaneous cytokine production was never observed. BMDM rapidly acquired the capacity to elaborate cytokine upon LPS activation. LPS-triggered BMDM were able to produce IL 1, IL 6, and TNF, throughout the culture period, although 2- to 3-week-old cells lost their ability to release IL 1 while accumulation of intracellular IL 1 remained unchanged. The dissociation between synthesis and release of IL 1 was not correlated with a significant modification of the specific binding of LPS onto the cell surface.
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PMID:Lipopolysaccharide-induced production of cytokines by bone marrow-derived macrophages: dissociation between intracellular interleukin 1 production and interleukin 1 release. 210 27


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