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)

Human mast cells are often found perivascularly and at mucosal sites and may play crucial roles in the inflammatory response. Recent studies have suggested a prominent role for mast cells in host defense. In this study, we analyzed the effects of a common airway pathogen, Moraxella catarrhalis and a commensal bacterium, Neiserria cinerea, on activation of human mast cells. Human mast cell leukemia cells (HMC-1) were activated with either phorbol myristate acetate (PMA) and calcium ionophore or with varying concentrations of heat-killed suspensions of bacteria. Supernatants were assayed for the cytokines interleukin-4 (IL-4), granulocyte macrophage colony stimulating factor (GM-CSF), IL-6, IL-8, IL-13 and monocyte chemotactic protein-1 (MCP-1). Nuclear proteins were isolated and assayed by electrophoretic mobility shift assay (EMSA) for nuclear factor kappaB (NF-kappaB) nuclear binding activity. In some experiments, NF-kappaB inhibitor, Bay-11 was added to determine functional significance. Both M. catarrhalis and N. cinerea induced mast cell activation and selective secretion of two key inflammatory cytokines, IL-6 and MCP-1. This was accompanied by NF-kappaB activation. Neither spun bacterial supernatants nor bacterial lipopolysaccharide induced cytokine secretion, suggesting need for direct bacterial contact with mast cells. Scanning electron microscopy revealed active aggregation of bacteria over mast cell surfaces. The NF-kappaB inhibitor, Bay-11, inhibited expression of MCP-1. These findings suggest the possibility of direct interactions between human mast cells and common bacteria and provide evidence for a novel role for human mast cells in innate immunity.
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PMID:Moraxella catarrhalis induces mast cell activation and nuclear factor kappa B-dependent cytokine synthesis. 1245 64

Interleukin (IL)-4, IL-10, and IL-13 affect monocyte/macrophage functions including regulation of cytokine production. We analyzed the regulatory effects of these cytokines on cytokine production using a human monoblastic cell line, UG3. It is interesting that IL-10 up-regulated, whereas IL-4 and IL-13 down-regulated monocyte chemoattractant protein-1 (MCP-1) production by unstimulated UG3 cells. IL-10-induced expression of MCP-1 mRNA occurred without de novo protein synthesis at transcriptional and post-transcriptional levels. The enhancement of binding activity of nuclear factor Sp1 (Sp-1) and signal transducer and activators of transcription (STAT)1 and 3 but not nuclear factor kappaB (NF-kappaB) was associated with this IL-10-induced MCP-1 expression. Furthermore, IL-10 suppressed lipopolysaccharide (LPS)-induced NF-kappaB binding but not Sp-1. The present results suggest IL-10 has two contrasting actions on the MCP-1 production of monocytes/macrophages, between the resting and activated conditions. The combination of activated Sp-1 and STATs is important for IL-10-induced MCP-1 expression in resting monocytes/macrophages, and the inhibition of LPS-induced NF-kappaB binding is crucial for down-regulation of MCP-1 by IL-10 in stimulated monocytes/macrophages.
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PMID:Interleukin-10 differently regulates monocyte chemoattractant protein-1 gene expression depending on the environment in a human monoblastic cell line, UG3. 1248 2

Dendritic cells (DC) are able to induce not only T helper 1 (Th1) but also Th2 immune responses after stimulation with allergens. While DC-derived interleukin (IL)-12 and IL-18 are the key factors for the induction of Th1 cells, early signals being involved in Th2 differentiation are less well characterized so far. To analyse such early signals we used an antigen-specific setting with CD4+ T cells from atopic donors stimulated in the presence of autologous mature DC, which were pulsed with different allergen doses. The addition of increasing amounts of allergen during DC maturation with tumour necrosis factor-alpha, IL-1beta and prostaglandin E2 resulted in enhanced secretion of IL-6 and IL-12 by DC followed by increased production of Th1 (interferon-gamma; IFN-gamma) as well as Th2 (IL-4, IL-5) cytokines by CD4+ T cells. The coculture of allergen-treated DC and CD4+ T cells also led to a dose-dependent expression of active signal transducer and activator of transcription-6 (STAT6), which was visible already after 1 hr. Additionally, rapid phosphorylation of STAT6 was seen in immature DC after stimulation with allergens but not with lipopolysaccharide or human serum albumin. STAT6 phosphorylation was associated with the production of IL-13 by DC. The addition of neutralizing anti-IL-13 antibodies during maturation of DC inhibited STAT6 phosphorylation in CD4+ T cells as well as the production of IL-4, and to a lesser extent of IL-5, while IFN-gamma production was not affected. Addition of exogenous IL-13 enhanced mainly the secretion of IL-4. Taken together, DC-derived IL-13, which is released after exposure to allergens appears to be one of the critical factors for DC to acquire the capability to induce Th2 cytokine production.
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PMID:Production of interleukin-13 by human dendritic cells after stimulation with protein allergens is a key factor for induction of T helper 2 cytokines and is associated with activation of signal transducer and activator of transcription-6. 1256 25

To determine the role of endogenous migration inhibitory factor (MIF) in regulation of immune response during murine cysticercosis caused by the helminth parasite Taenia crassiceps, we analyzed the course of T. crassiceps infection in MIF(-/-) BALB/c mice. MIF(-/-) mice were highly susceptible to T. crassiceps and developed significantly higher parasite loads compared to similarly infected MIF(+/+) mice. Throughout the course of infection, Taenia crassiceps soluble antigen-stimulated spleen cells from both MIF(+/+) and MIF(-/-) mice produced significant and comparable levels of interleukin-4 (IL-4), but those from MIF(-/-) mice produced significantly more IL-13, as well as gamma interferon (IFN-gamma), suggesting that the susceptibility of MIF(-/-) mice to T. crassiceps was not due to the lack of IFN-gamma production. Interestingly, low levels of both total and specific immunoglobulin G2a were observed in MIF(-/-) cysticercotic mice despite the high IFN-gamma levels; in addition, peritoneal macrophages obtained from T. crassiceps-infected MIF(-/-) mice at different time points failed to respond efficiently to stimulation in vitro with lipopolysaccharide plus IFN-gamma and produced significantly lower levels of IL-12, tumor necrosis factor alpha, and NO compared to those from MIF(+/+) mice. These findings demonstrate that MIF plays a critical role in mediating protection against T. crassiceps in vivo. Moreover, these findings also suggest that impaired macrophage function rather than the lack of Th1 development may be responsible for mediating susceptibility to T. crassiceps.
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PMID:Macrophage migration inhibitory factor plays a critical role in mediating protection against the helminth parasite Taenia crassiceps. 1259 39

Interleukin (IL)-13 has recently been shown to play important and unique roles in asthma, parasite immunity, and tumor recurrence. At least two distinct receptor components, IL-4 receptor (R)alpha and IL-13Ralpha1, mediate the diverse actions of IL-13. We have recently described an additional high affinity receptor for IL-13, IL-13Ralpha2, whose function in IL-13 signaling is unknown. To better appreciate the functional importance of IL-13Ralpha2, mice deficient in IL-13Ralpha2 were generated by gene targeting. Serum immunoglobulin E levels were increased in IL-13Ralpha2-/- mice despite the fact that serum IL-13 was absent and immune interferon gamma production increased compared with wild-type mice. IL-13Ralpha2-deficient mice display increased bone marrow macrophage progenitor frequency and decreased tissue macrophage nitric oxide and IL-12 production in response to lipopolysaccharide. These results are consistent with a phenotype of enhanced IL-13 responsiveness and demonstrate a role for endogenous IL-13 and IL-13Ralpha2 in regulating immune responses in wild-type mice.
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PMID:Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha 2. 1264 99

Endotoxin (lipopolysaccharide, LPS) inducible cytokine release by human whole blood is increasingly used to model inflammatory responses in vitro, to detect the presence of pyrogenic contaminations as well as to monitor disease states or immunomodulatory treatments ex vivo. However, the LPS-stimulated blood model primarily allows the assessment of monocyte responses. Here, a whole blood model was established which allows assessment of lymphocyte responses. Four different superantigens, namely staphylococcal enterotoxin A and B (SEA, SEB), toxic shock syndrome toxin-1 (TSST-1) or streptococcal exotoxin A (SPEA) were tested with respect to the induction of lymphokine release. All superantigens were capable of inducing significant amounts of the lymphokines interferon-gamma (IFNgamma), interleukin 2 (IL-2), IL-4, IL-5, IL-13 and tumor necrosis factor beta (TNFbeta) after 72 h of incubation. Concentration-dependencies and kinetics were determined. Blood from 160 healthy donors was used to assess the variability of SEB-inducible lymphokine release. Interindividual differences were more pronounced compared to LPS-inducible monokine release. However, the individual response was maintained when blood from six donors was tested once a week for 8 weeks, suggesting that the individual response represents a donor characteristic. The model appears to be suitable for the evaluation of immunomodulatory agents in vitro as well as ex vivo.
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PMID:A model of human whole blood lymphokine release for in vitro and ex vivo use. 1266 71

In the present report we have analyzed whether human normal cord blood-derived mast cells (CBMC) could interact with bacterial products, especially lipopolysaccharide (LPS) from Escherichia coli and peptidoglycan (PGN) from Staphylococcus aureus, known as Toll-like receptor (TLR) 4 and TLR2 agonists, respectively. We found that both LPS and PGN induced significant release of not only tumor necrosis factor-alpha (TNF-alpha), but also IL-5, IL-10 and IL-13 by human mast cells (MC). We also established that the stimulation of CBMC with LPS or with PGN is mediated through interactions with TLR4 or with TLR2, respectively. Thus, our data indicate that activation of either TLR2 or TLR4 pathway may lead to a pro-Th2 immune response. However, the release of TNF-alpha induced by LPS, conversely to PGN, required the priming of CBMC by IL-4 and the presence of serum components, in particular soluble CD14. Of interest, stimulation by PGN, but not by LPS, induced release of histamine by human MC. Altogether, these findings provide the first evidence that human MC differentially respond towards bacterial components, and that their responses depend on TLR pathways and reveal human specificities in the pattern of cytokine production.
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PMID:Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells. 1267 55

Recent studies indicate that normal B cells can be primed to differentiate into two distinct cytokine-secreting effector subsets, Be1 and Be2. The aim of this study was to analyse, for the first time, Be1 and Be2 cells at the single cell level in SLE patients using the recently developed technique of flow cytometry for intracellular cytokines. Peripheral blood mononuclear cells (PBMC) from SLE patients and age- and sex-matched normal controls were cultured for 24 h in the presence or absence of phorbal myristate acetate and ionomycin (PMA/I) or lipopolysaccharide (LPS). The production of type I (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-6, IL-10, IL-13) cytokines by B cells (and IL-10 production by fractionated CD5+ and CD5- B cells) was investigated using an intracellular cytokine staining technique and flow cytometry. In the absence of PMA/I stimulation, the percentage of B cells from SLE patients was significantly lower than those of normal subjects and significantly more SLE B cells spontaneously produced IL-10 than controls. Moreover, CD5+ B cells from SLE patients were enriched for cells with signs of previous in vivo activation and for high levels of IL-10 production. A significant positive correlation was observed between the percentage of IL-10- and IL-6-producing PMA/I-stimulated B cells in SLE patients, but not in controls. There were no significant differences in the production of other cytokines by B cells of SLE patients and normal subjects. In conclusion, a general alteration of type 1 and type 2 cytokine production by B cells is not observed in SLE patients. The role of B cell cytokines in the pathogenesis of SLE appears to be exerted by elevated secretion of in vivo IL-10, which may play an important role in the immune dysregulation observed in SLE patients. Moreover, the cross regulation of IL-10 and IL-6 is disrupted in SLE patients.
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PMID:Assessment of Be1 and Be2 cells in systemic lupus erythematosus indicates elevated interleukin-10 producing CD5+ B cells. 1276 98

The effects of exposure to placental malaria infection on newborn immunological responses, in particular Th1/Th2 cytokines and antigen-presenting cell (APC) function, were compared between cord blood mononuclear cells (CBMC) from parasitized and non-parasitized placentas of Gambian women. Cells were analysed in vitro for their ability to respond to mitogens [phorbol myristate acetate (PMA)/ionomycin, phytohaemagglutinin (PHA)], a malaria-unrelated test antigen [purified protein derivative of Mycobacterium tuberculin[purified protein derivative (PPD)] and Plasmodium falciparum schizont extracts. Mitogens induced strong proliferation and secretion of high concentrations of both IL-13 and sCD30 in CBMC from both groups. Conversely, significantly lower amounts of IFN-gamma were induced in the parasitized group in response to low doses of PHA. Protein antigens induced very low amounts of all tested cytokines, in particular IFN-gamma. However, a significantly higher release of sCD30 was observed in response to schizont extracts in the parasitized group. Addition of LPS to activate APC to low doses of PHA or schizont extracts increased the IFN-gamma production in both groups but levels remained lower in CBMC from the parasitized group. This result correlates with the lower production of IL-12 found following lipopolysaccharide (LPS) stimulation in this group. Taken together, these data show that placental infection with P. falciparum affects Th1 differentiation and sCD30 priming of neonatal lymphocytes and that the probable mode of action is via APC.
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PMID:Plasmodium falciparum infection of the placenta affects newborn immune responses. 1293 Mar 69

Several studies have shown that exposure to bacterial lipopolysaccharide (LPS) can either prevent or inhibit asthma in humans and laboratory rodents. Much emphasis has been placed on the role of cytokines and chemokines in the establishment and maintenance of allergic airway disease. Therefore, it is of interest to study the role of LPS in affecting airway pathology and lung cytokine and chemokine responses in the maintenance phase of asthma. Increasing doses of LPS were administered into the airways of mice presensitized with cockroach allergen (CRAg), then allergic airway disease parameters were assessed after CRAg challenge. Airway hyperresponsiveness after antigen challenge decreased at the highest dose of LPS tested, which was accompanied by a decrease in airway and lung eosinophils. However, a dramatic increase in lung inflammation because of neutrophil influx was observed. Measurement of cytokines in lungs of LPS-treated, CRAg-sensitized mice indicated that interleukin (IL)-12 levels were increased by LPS treatment in a dose-dependent manner, as were levels of several inflammatory chemokines. In contrast, levels of IL-4, IL-13, IL-5, and IL-10 were reduced in whole lung homogenates only of high-dose LPS-treated mice. Intranasal administration of neutralizing anti-IL-12 at the time of high-dose LPS challenge reduced lung IL-12, interferon-gamma, CXCL9, and CXCL10 but did not affect levels of the other chemokines or Th2-type cytokines, and did not restore AHR. These findings suggest that the amelioration of airway hyperresponsiveness observed in LPS-treated, CRAg-sensitized mice is coincident with an immune deviation of the lung inflammatory response, independent of IL-12.
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PMID:Interleukin-12-independent down-modulation of cockroach antigen-induced asthma in mice by intranasal exposure to bacterial lipopolysaccharide. 1457 95


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