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)

Simple methods for obtention of primary cultures of isolated astrocytes and microglia from adult simian brain have been developed. Characterization of these two glial cell populations were performed by morphological observations and by immunocytochemistry. The astroglial cultures were obtained by an indirect method. After L-leucine methyl-ester treatment and trypsinizations, more than 99% of cells expressed glial fibrillary acidic protein (GFAP), whereas no macrophages or microglia could be detected. Likely, the 1% remaining cells were immature astrocytes or cells that lost their GFAP expression. Cultured simian astrocytes expressed vimentin, laminin, and fibronectin. We also found a constitutively low expression of major histocompatibility complex (MHC) class II by cultured astrocytes which was significantly enhanced by lipopolysaccharide (LPS), interferon gamma (IFN-gamma), or tumor necrosis factor alpha (TNF-alpha) treatments. Microglial cultures were obtained by a direct method of isolation using Percoll gradient separations and compared to simian monocyte-derived macrophages or alveolar macrophages. Microglial cells differed from macrophages by their proliferation upon granulocyte-macrophage colony stimulating factor (GM-CSF) treatment and by their typical morphology when observed by scanning electron microscopy. As macrophages, they expressed in vitro CD68, CD64, CD14, CD11b, MHC class II, and fibronectin. However, contrary to macrophages, simian cultured microglia expressed laminin. This observation suggests that microglia represent a new potential source of this extracellular matrix protein in the brain.
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PMID:Obtention and characterization of primary astrocyte and microglial cultures from adult monkey brains. 930 79

We studied the capacity of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) to modulate monocyte anti-leukaemic activity when administered to patients following myelosuppressive chemotherapy. The leukaemic cell lines K562, U937 and KG-1 were used as models of human leukaemia as they exhibit differential sensitivity to cell-mediated or TNF-mediated cytotoxicity. Monocyte tumouricidal activity was augmented by rhGM-CSF or lipopolysaccharide (LPS) alone in vitro against leukaemic blasts, whereas granulocyte-colony stimulating factor (rhG-CSF) was without effect. rhGM-CSF and LPS exhibited an additive effect in stimulating the cytotoxic effect of monocytes against K562 blasts compared with either agent alone (P < 0.001). Both cell-mediated and soluble TNF-mediated killing of leukaemic blasts was augmented by rhGM-CSF administration to patients following chemotherapy. This effect persisted for up to 4 weeks after cessation of GM-CSF therapy. The administration of rhGM-CSF significantly increased the anti-leukaemic activity of monocytes against leukaemic targets that were resistant to secreted TNF, probably via a transmembrane TNF-dependent mechanism. Therapy with rhG-CSF exhibited a minimal effect. We conclude that administration of rhGM-CSF, but not rhG-CSF, augments the tumouricidal properties of the monocyte-macrophage system, particularly during recovery from myelosuppressive chemotherapy. Moreover, the killing mechanism is direct and not mediated by an antibody-dependent cellular cytotoxic (ADCC) mechanism. Killing of TNF-resistant leukaemic cells in particular may be augmented via cell-to-cell contact.
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PMID:Monocyte-mediated killing of human leukaemia is enhanced by administration of granulocyte-macrophage colony stimulating factor following chemotherapy. 932 96

Leukaemia inhibitory factor (LIF) acts on the growth and differentiation of haematopoietic cells. By using a specific enzyme-linked immunosorbent assay for human LIF, we demonstrate that human bone marrow stromal cells produce LIF. LIF synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMAS). LIF production in response to PMA is PKC-dependent since the two PKC inhibitors sphingosine and staurosporine markedly diminished it. Interleukin 1alpha (IL-1alpha), IL-1beta, IL-3, IL-6, IL-8, tumour necrosis factor (TNF-alpha) and SCF (both at 10 ng/ml) stimulate LIF production. By contrast macrophage colony-stimulating factor (M-CSF), granulocyte (G)-CSF, GM-CSF, basic fibroblast growth factor (bFGF), platelet-activating factor (PAF), protaglandin E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4 (LTC4) did not. These results suggest that bone marrow stromal cells might represent a major source for the cytokine-regulated local production of LIF inside human bone marrow.
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PMID:Spontaneous and inducible production of leukaemia inhibitory factor by human bone marrow stromal cells. 934 7

Neutrophils play a key role in the pathophysiology of septic multiple organ dysfunction syndrome (MODS) through excessive release of toxic granule components and reactive oxygen metabolites with consequent tissue destruction. The increase of senescent neutrophils during sepsis indicates a potential breakdown of autoregulatory mechanisms including apoptotic processes to remove activated neutrophils from inflammatory sites. Therefore, neutrophil apoptosis of patients with severe sepsis and its regulatory mechanisms were investigated. Spontaneous neutrophil apoptosis from patients with severe sepsis was significantly reduced in comparison to healthy individuals. Cytokines detected in the circulation during sepsis (tumor necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma], granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) inhibited neutrophil apoptosis in both groups, though the effect was more distinct in neutrophils from healthy humans. Addition of lipopolysaccharide (LPS) to neutrophils from healthy humans markedly (P < .05) reduced apoptosis which was partially restored through addition of anti-TNF-antibody. Interleukin-10 (IL-10) counteracted (P < .05) inhibition of neutrophil apoptosis induced by LPS, recombinant human (rh) TNF-alpha, rhIFN-gamma, rhG-CSF, and rhGM-CSF, whereas rhIL-4 or rhIL-13 were ineffective. Reduced neutrophil apoptosis during sepsis was concomitant with increased tyrosine phosphorylation, while IL-10 markedly inhibited tyrosine phosphorylation in LPS-stimulated neutrophils. These results identify proinflammatory cytokines and IL-10 as strong regulators of spontaneous neutrophil apoptosis during sepsis. Inhibition as well as acceleration of neutrophil apoptosis seems to be associated with alterations of signal transduction pathways.
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PMID:Interleukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. 934 17

Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investigated the effects of PGE2 on human dendritic cells (DCs) which develop in the presence of GM-CSF and IL-4. We demonstrate that in the absence of LPS, PGE2 dose dependently stimulated the production of IL-12 by DCs. Although PGE2 alone stimulated the production of low amounts of IL-12 only, it synergized with tumor necrosis factor (TNF)-alpha to induce high levels of IL-12 production by DCs. Addition of TNF-alpha in the absence of PGE2 had no effect on IL-12 production. Conversely, in the presence of LPS, PGE2 inhibited IL-12 production by DCs in a dose-dependent manner. The combination of PGE2 and TNF-alpha efficiently silenced mannose receptor-mediated endocytosis in DCs and readily induced neo-expression of the CD83 antigen. In addition, the expression of various surface antigens such as major histocompatibility complex class I and II, adhesion, as well as costimulatory molecules was upregulated by this treatment. The effects of PGE2 on IL-12 synthesis and CD83 expression could be mimicked by dibutyryl-cAMP and forskolin, indicating that they were due to the intracellular elevation of cAMP levels. DC treated with PGE2 and TNF-alpha were most potent in stimulating allogeneic T cell proliferation. Our data demonstrate that PGE2 contributes to the maturation of human DCs and that PGE2 can be a potent enhancer of IL-12 production by human DCs.
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PMID:Prostaglandin E2 and tumor necrosis factor alpha cooperate to activate human dendritic cells: synergistic activation of interleukin 12 production. 934 19

A quantitative and kinetic study of the release of the hematopoietic cytokines IL-3, IL-5 and GM-CSF, the immunoregulatory cytokine IL-12 heterodimer (and its p40 subunit) and IL-13 by human peripheral blood mononuclear cells (PBMC) stimulated in vitro with the superantigen streptococcal pyrogenic (erythrogenic) exotoxin A (SPE A) from Streptococcus pyogenes is reported. PBMC were stimulated in parallel with heat-killed group A streptococcal cells, E. coli lipopolysaccharide (LPS) and with concanavalin A (Con A) in certain experiments for comparative purposes. The cytokines were assayed in the supernatant fluids by ELISA. IL-13 expression was also determined by a quantitative competitive PCR. IL-3, IL-5, GM-CSF, IL-12 p40, IL-12 heterodimer and IL-13 expression was induced by SPE A in a time- and dose-dependent manner in rather substantial amounts except the IL-12 heterodimer, which was released in small quantities. In contrast to SPE A, IL-3, IL-5 and IL-13 were not or poorly elicited by streptococcal cells or LPS whereas these two stimulants induced relatively high amounts of GM-CSF. Interestingly, both IL-12 p40 and IL-12 heterodimer were released in much higher amounts by streptococcal cells. Con A induced IL-3, IL-5, GM-CSF and IL-13 production in amounts comparable to those elicited by SPE A. The possible pathophysiological relevance of the elicitation by SPE A and streptococcal cells of these cytokines is discussed.
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PMID:Streptococcal pyrogenic exotoxin A (SPE A) superantigen induced production of hematopoietic cytokines, IL-12 and IL-13 by human peripheral blood mononuclear cells. 940 4

Thalidomide has been shown to selectively inhibit TNF-alpha production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-alpha has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-alpha and other cytokines and on animal survival. After injection of 100-350 micrograms LPS into mice, cytokines including TNF-alpha, IL-6, IL-10, IL-1 beta, GM-CSF and IFN-gamma were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-alpha levels were reduced by 93%, in a dose-dependent manner, and TNF-alpha mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1 beta, or IFN-gamma. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 micrograms to 300 micrograms in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death.
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PMID:Thalidomide protects mice against LPS-induced shock. 949 38

In the present study the role of granulocyte-macrophage colony stimulating factor (GM-CSF) in the reduced toxoplasmastatic activity of monocytes was investigated in patients with acquired immunodeficiency syndrome (AIDS). The secretion of GM-CSF by non-stimulated monocytes and by Toxoplasma gondii-infected monocytes from AIDS patients did not differ from that of healthy individuals. Furthermore, GM-CSF was not detected in sera from AIDS patients and healthy individuals. However, upon stimulation with lipopolysaccharide (LPS), monocytes from AIDS patients released significantly more GM-CSF than those from healthy individuals. Incubation of monocytes from AIDS patients with polyclonal antibodies against GM-CSF restored their inhibitory activity against T. gondii. On the basis of the present and earlier results the putative mechanism of reduced toxoplasmastatic activity of monocytes from AIDS patients may be as follows: upon stimulation with human immunodeficiency virus (HIV) the increased synthesis of GM-CSF by monocytes stimulates the production of prostaglandin E2 (PGE2) which, in turn, impairs the toxoplasmastatic activity of these cells.
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PMID:Reduced toxoplasmastatic activity of monocytes from AIDS patients: a role for granulocyte-macrophage colony-stimulating factor. 949 93

In human tissues different populations of dendritic cells (DC) emerge from hematopoietic progenitor cells (HPC) in the bone marrow, with the intermediate steps of differentiation not being completely understood. In vitro, DC can be directly obtained from HPC or from blood monocytes (MO) cultured in the presence of GM-CSF and additional cytokines. We compared the antigenic profile of DC derived from either MO or HPC and studied their capacity to stimulate naive lymphocytes (LY) in the allogeneic mixed lymphocyte reaction. Both types of DC expressed high levels of CD1a, MHC class II, CD80, CD86 and CD40 and were potent stimulators of LY proliferation. DC of HPC origin, though, induced a stronger mixed lymphocyte reaction than MO-derived DC and showed a slightly higher average expression of costimulatory antigens. Low-level expression of CD14 did not negatively correlate with DC function on DC stimulated with lipopolysaccharide and was even slightly higher expressed on DC differentiating from HPC than on DC from CD14+ MO.
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PMID:Comparative analysis of dendritic cells derived from blood monocytes or CD34+ hematopoietic progenitor cells. 956 69

Dendritic cells (DC) are potent antigen presenting cells, which are responsible for the initiation of naive T and T-dependent immune responses. The present studies were based upon recent reports that commercial collagen I preparations induce the maturation of human DC in vitro. We show that human blood monocyte-derived (GM-CSF and IL-4 cultured) DC pulsed on collagen I-coated plates undergo a dose-dependent increase in stimulatory capacity in oxidative mitogenesis assays. This is accompanied by the upregulation of costimulatory molecules (CD40, CD80, CD86), CD25, ICAM-1 and the DC-specific marker CD83. The maturation effect is more potent than TNF-alpha, which is a known mediator of DC function. However, bacterial lipopolysaccharide (LPS), a powerful inducer of DC maturation, was found to be present at very high levels in one commercial collagen solution that was tested. The effect of LPS upon DC maturation was similar to culture with collagen. Furthermore, a different collagen I preparation with low levels of LPS contamination was less effective at inducing DC maturation, while spiking the collagen solution with LPS prior to plastic coating equalised these effects. Finally, human monocyte-derived DC were found not to express typical collagen receptors VLA-1, 2 and 3. We therefore propose that LPS contamination may at least partially explain reported collagen I induced DC maturation.
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PMID:Bacterial lipopolysaccharide contamination of commercial collagen preparations may mediate dendritic cell maturation in culture. 969 67


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