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)

In this brief definitive report, we show that over a 6-h period and under serum-free conditions, recombinant monocyte-macrophage colony-stimulating factor 1 (rCSF-1) and lipopolysaccharide (LPS) synergize and induce macrophages to express higher levels of mRNA for interleukin 1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 and to release more bioactivity than macrophages treated with LPS alone. This synergy was regulated by the amount of LPS in the culture medium. Paraformaldehyde-fixed macrophages like-wise showed augmentation of IL-1 activity, but whereas all of the bioactivity associated with the fixed macrophages could be neutralized by anti-IL-1 alpha antibody only approximately 40% of the supernate activity could be attributed to IL-1 alpha. Preliminary data suggest that the augmenting effect induced by CSF-1 cannot be explained solely on a quantitative basis because the addition of rIL-1 alpha to supernates of macrophages treated with LPS alone or with the combination of LPS and CSF-1 resulted in an increase in thymocyte mitogenic activity to a level that could not be explained on an additive basis. Although the supernates contained TNF and IL-6, antibody neutralization assays made it unlikely that these were directly responsible for the augmenting effect. These results suggest that CSF-1 not only enhances basic genetic responses induced by LPS alone but also may induce a mechanism that amplifies cytokine bioactivity.
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PMID:Synergistic interaction of bacterial lipopolysaccharide and the monocyte-macrophage colony-stimulating factor: potential quantitative and qualitative changes in macrophage-produced cytokine bioactivity. 137 Dec 99

Impaired production and delivery of neutrophils to the site of infection have been implicated in the increased susceptibility of the neonate to infection. Because granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) play critical roles in the production of neutrophils from marrow precursors, we assessed the ability of leukocytes from neonates and adults to produce GM-CSF, G-CSF, and, for comparison, macrophage colony-stimulating factor (M-CSF) after stimulation with concanavalin A +/- phorbol myristate acetate [blood mononuclear cells (MC) and T lymphocytes] or lipopolysaccharide (monocytes). MC and monocytes from adult and neonatal subjects produced mRNA for GM-CSF, G-CSF, and M-CSF, whereas T cells produced only GM-CSF mRNA. Neonatal MC and T cells accumulated only approximately 30% as much GM-CSF mRNA as did adult MC and T cells. In contrast, the accumulation of GM-CSF mRNA by neonatal and adult monocytes was similar. Neonatal MC also accumulated similar amounts of G-CSF mRNA and somewhat more M-CSF mRNA than did adult MC; results with monocytes were similar to those with MC. Results of colony-stimulating activity bioassays on supernatants from neonatal and adult MC stimulated with concanavalin A paralleled the mRNA results.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased granulocyte-macrophage colony-stimulating factor production by human neonatal blood mononuclear cells and T cells. 137 32

Exogenous interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta) (type I IFNs) are known to suppress the IFN-gamma-dependent expression of class II MHC (Ia) antigens on macrophages (M phi). We report here that the endogenous type I IFNs produced by M phi in response to IFN inducers regulate Ia expression of the M phi themselves. Coculture of M phi with IFN-gamma and polyinosinic-polycytidylic acid [poly(I):poly(C)] resulted in the reduction of Ia expression in comparison with those cultured without poly(I):poly(C). Pretreatment of M phi with poly(I):poly(C) or a bacterial lipopolysaccharide (LPS), which is also a potent IFN inducer, in vitro or in vivo, before being exposed to IFN-gamma was also effective in suppressing the Ia expression. Such suppression was abolished by the addition of anti-IFN-alpha/beta antibodies to the M phi culture along with IFN-gamma. M phi cultured with L-cell conditioned medium (LCM) containing M-CSF were less capable of expressing Ia antigens than those cultured without LCM. The Ia-expressing ability of LCM-treated M phi was also restored by the addition of anti-IFN-alpha/beta antibodies. M phi in the early stage of sterile inflammation were less responsive to IFN-gamma than those in the late stage. These results suggest that endogenous type I IFNs, which are produced in response to natural or synthetic IFN-inducers, regulate M phi Ia expression in an autocrinal manner.
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PMID:Suppression of macrophage Ia antigen expression by endogenous interferon-alpha/beta. 137 84

Histamine and putrescine (a precursor of polyamines) are formed by histidine decarboxylase (HDC) and ornithine decarboxylase (ODC), respectively. Within a few hours after injection of a lipopolysaccharide (LPS) into mice, HDC is induced in the liver, spleen, lung and bone marrow, and ODC is induced in the liver, spleen and bone marrow. Since LPS is known to stimulate the production of various cytokines, the abilities of various cytokines to induce HDC and ODC in the tissues of mice were examined. IL-2, IL-6, IL-8, IFN gamma and M-CSF were ineffective. IL-1 alpha, IL-1 beta, TNF alpha and TNF beta induced HDC and ODC, as does LPS. On the other hand, GM-CSF and G-CSF induced HDC and ODC only in the spleen and bone marrow within a few hours after their injection. These results suggest that, in addition to their roles in inflammation or immune responses, HDC and ODC are also involved in an early stage of hematopoiesis.
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PMID:GM-CSF and G-CSF stimulate the synthesis of histamine and putrescine in the hematopoietic organs in vivo. 138 20

Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of a number of lympho-haemapoietic cytokines, including CSF-1, interleukin-6 (IL-6) and leukaemia inhibitory factor (LIF) now known to be synthesized by epithelial cells in the murine uterus. GM-CSF synthesis is regulated primarily by the ovarian steroid hormone oestrogen, but is also subject to modulation by factors including a seminal component of seminal vesicle origin which stimulates a 20-fold increase in luminal fluid content at mating, and bacterial lipopolysaccharide (LPS) and the T-lymphocyte and natural killer (NK) cell product interferon-gamma (IFN gamma). In the non-pregnant mouse GM-CSF synthesis peaks at oestrus. Synthesis is maintained at comparable or moderately higher levels during the preimplantation period of pregnancy and in the non-decidualized endometrium during mid gestation. An embryotrophic activity is suggested by studies in vitro that indicate that GM-CSF stimulates attachment and outgrowth of blastocysts. It is postulated that GM-CSF is of major importance to the physiology of pregnancy through its role as a component of a local cytokine circuit acting to recruit and regulate function of endometrial leukocytes, and by its action as interlocutor and important effector arm in embryo-maternal interactions during gestation.
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PMID:Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus. 146 94

L929 culture medium (a source of macrophage colony stimulating factor (M-CSF) or recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF)-derived bone marrow macrophages treated with cisplatin or lipopolysaccharide (LPS) (10 micrograms/ml) were effective in the production of L-arginine-dependent reactive nitrogen intermediates (RNI) and generation of tumouricidal activity. The abilities of RNI secretion and related tumouricidal activity against P815 mastocytoma cells were compared. These parameters were found to be closely correlated in various experiments. RNI secretion and generation of bone marrow macrophage-mediated tumouricidal activity were significantly inhibited by L-N-monomethyl arginine (L-NMMA), a specific inhibitor of the L-arginine pathway, but L-NMMA did not inhibit macrophage-mediated killing of tumour necrosis factor (TNF)-sensitive Wehi cells, suggesting that activated macrophages exhibit at least two cytolytic mechanisms, one by L-arginine-dependent nitric oxide pathway and another by TNF-mediated killing. The present findings suggest that the mechanism of tumour cell killing by activated macrophages may differ, depending on the tumour cell type, and reactive nitrogen intermediates play a major role in cisplatin-mediated activation of bone marrow-derived macrophages.
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PMID:Production of reactive nitrogen intermediates by bone marrow-derived macrophages on treatment with cisplatin in vitro. 151 67

A recently identified novel mammalian cyclin (CYL1), induced by growth factors and apparently functional during the G1 phase of the cell cycle, is of potential significance, given that cell division is primarily controlled in G1. We have measured CYL1 gene expression in murine bone marrow-derived macrophages (BMM), a normal cell type dependent upon colony-stimulating factors (CSFs) for survival and proliferation. The induction of CYL1 mRNA levels correlated strongly with stimulation of DNA synthesis, since elevated CYL1 mRNA levels occurred in response to the mitogenic stimuli, CSF-1, and granulocyte/macrophage CSF, but not to nonmitogenic macrophage-activating agents. BMM are subject to cell cycle arrest by numerous agents, including tumor necrosis factor alpha, interferon gamma, bacterial lipopolysaccharide, and agents that increase cAMP. These antiproliferative agents suppressed CSF-1-stimulated CYL1 gene expression, even when added late in G1. This pattern of CYL1 gene expression was remarkably consistent with the ability of these agents to inhibit progression into S phase. The mechanisms of negative growth regulation are largely unknown, and given the likely importance of G1 cyclins in the control of cell division, we propose that antiproliferative agents may exert their effects by suppressing G1 cyclin gene expression.
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PMID:Suppression of growth factor-induced CYL1 cyclin gene expression by antiproliferative agents. 153 6

It has been reported that the granulocyte-derived hematoregulatory pentapeptide, HP-5, and its dimer (HP-5b) have potent hematoregulatory properties. The proposed mechanism of action for HP-5b is synergy with colony-stimulating activity (CSA) resulting in enhanced myeloid colony formation in vitro. We now demonstrate that the effects of HP-5b on enhanced colony formation are indirect and mediated by an effect on CSA production by bone marrow stromal cells. Bone marrow stromal cell culture systems from mice, rats, and humans were used as target cells for the action of HP-5 monomer and dimer. Cell-free supernatants from these cultures were assayed for CSA in a murine granulocyte-macrophage colony-forming unit (CFU-GM) assay. Supernatants from stromal cell cultures pulsed for 1 h with HP-5b resulted in increased murine CFU-GM colony proliferation with an estimated half-maximal effective concentration (EC50) of 1-5 ng/ml. This increase in CFU-GM proliferation was neutralized by anti-macrophage colony-stimulating factor (anti-M-CSF) antibodies. The HP-5 monomer was without effect on constitutive CSA production by stromal cells, but it antagonized HP-5b-induced CSA production in a dose-responsive manner with an estimated half-maximal inhibitory concentration (IC50) of 0.2-0.4 ng/ml. The ability of HP-5 monomer to antagonize HP-5b induction of CSA appears specific in that HP-5 monomer failed to alter interleukin 1 (IL-1) or lipopolysaccharide (LPS)-induced stromal cell CSA production.
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PMID:Regulation of colony-stimulating activity production from bone marrow stromal cells by the hematoregulatory peptide, HP-5. 154 91

Keratinocytes produce multiple cytokines in response to a variety of stimuli. The release of interleukin 1 (IL-1) from keratinocytes may be significant in initiation of cutaneous inflammation, and the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) is thought to be important in the regulation of antigen-presenting function by epidermal Langerhans cells. Because cyclosporin inhibits interleukin 2 release from T cells, it has been suggested that cyclosporin may function as an anti-inflammatory agent within the epidermis through inhibition of keratinocyte cytokine release. This investigation examined the direct effect of cyclosporin on the production of GM-CSF by murine keratinocytes and the keratinocyte cell line PAM 212. GM-CSF bioactivity increased in cell supernatants from keratinocytes exposed in vitro to 1 microgram/ml cyclosporin for up to 24 h. GM-CSF and IL-1 mRNA levels in keratinocytes cultured under similar conditions or in the presence of lipopolysaccharide also increased. The lack of inhibition of GM-CSF expression following cyclosporin treatment is consistent with recent observations in T cells and is opposite to the effect of cyclosporin on interleukin 2.
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PMID:Cyclosporin increases granulocyte/macrophage colony-stimulating factor (GM-CSF) activity and gene expression in murine keratinocytes. 154 36

The present study was designed to establish that the factor increasing monocytopoiesis (FIM) is a unique factor that differs from interleukin 1 (IL-1) and macrophage colony-stimulating factor (M-CSF) in its effect on the production of granulocytes, lymphocytes, and monocytes in C3H/HeJ mice, which are unresponsive to lipopolysaccharide. [3H]thymidine, together with the cytokine under study, was used as a marker for newly formed cells. The number of each category of labeled leukocytes in the circulation was calculated from the number of leukocytes per microliter of blood, differential counts of the leukocytes, and their labeling indices, as determined by autoradiography. To compare the effect of the various cytokines on the production of leukocytes, the area under the curve (AUC) of the number of each category of leukocytes over a period of 96 h has been calculated. The results show that IL-1 causes, within 2 h, an increase in the number of circulating granulocytes, most probably by recruitment of these cells from the storage pool in the bone marrow and the marginating pool in the blood vessels. This is followed by an increased production of granulocytes; the production of monocytes and lymphocytes is not affected by IL-1. Administration of M-CSF had no significant effect on the production of granulocytes, lymphocytes, or monocytes in vivo. FIM specifically stimulated the production of monocytes and had no effect on the other cell lineages. Because FIM is synthesized and secreted by macrophages upon phagocytosis at the site of an inflammation, this study indicates that FIM is a monokine that acts as a long-range regulator to signal the bone marrow to increase monocyte production during an acute demand for more monocytes and (exudate) macrophages.
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PMID:Effect of interleukin 1, macrophage colony-stimulating factor, and factor increasing monocytopoiesis on the production of leukocytes in mice. 157 96


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