UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of cytokines by human conjunctival epithelial cells following stimulation was investigated. Primary cultures of human conjunctival epithelial cells were characterized by morphology and keratin expression. Cultured epithelial cells were treated with varying concentrations of lipopolysaccharide, interleukin (IL)-1 beta, calcium ionophore A23187, or phorbol myristate acetate, and cytokine secretion was determined over specified intervals. Culture supernatants and cell lysates were analyzed by ELISA for IL-1 beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-11, IL-1 receptor antagonist (IL-1ra), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF). With the exception of IL-1ra, unstimulated conjunctival epithelial cells produced cytokines at relatively low or undetectable levels. IL-1ra was detected in both culture supernatants and cell lysates under basal conditions. In response to stimuli, conjunctival epithelial cells secreted the proinflammatory cytokines TNF-alpha, IL-6, IL-8, and GM-CSF in a dose- and time-dependent fashion. After stimulation, the intracellular levels of IL-1ra increased in these cells but the supernatant-associated levels remained unchanged. None of the other cytokines evaluated (IL-1 beta, IL-3, IL-4, IL-5, and IL-11) were detected in supernatants or lysates of resting or stimulated cells. These findings suggest that conjunctival epithelial cells may contribute to the pathogenesis of human ocular diseases by production of proinflammatory cytokines. Further evaluation of these cells as targets of therapy is warranted.
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PMID:Secretion of proinflammatory cytokines by human conjunctival epithelial cells. 923 76

Dietary exposure to vomitoxin (VT) results in hyperelevated serum IgA and IgA nephropathy in mice. To assess the possible role of cytokines in this IgA dysregulation, the effects of a single oral exposure in B6C3F1 male mice to 0, 5 or 25 mg/kg BW VT on production of IgA and cytokines in Peyer's patch (PP) and spleen cell cultures were evaluated. IgA levels were increased significantly in PP cell cultures prepared from mice at 2 or 24 h after oral exposure to VT and subsequently stimulated with phorbol myristate acetate (PMA) and ionomycin (ION) or with lipopolysaccharide (LPS). Significant effects on IgA production were not observed in spleen cell cultures. Since cytokines such as IL-2, IL-4, IL-5 and IL-6 have been shown to promote IgA production, the effect of the same VT exposure regimen on secretion of these mediators was determined in PP and spleen cultures. Supernatant IL-2 and IL-4 levels were unaffected by the prior treatment of animals with VT. In contrast, IL-5 levels were increased significantly in 7-day PP cell cultures obtained 2 h after VT exposure both with and without PMA + ION exposure but not in other cultures. IL-6 levels were increased significantly in LPS-treated cultures prepared from PP at 2 and 24 h following exposure to VT. IL-6 levels were also elevated significantly in both PMA + ION or LPS treated cultures from spleen isolated at 2 h but not 24 h post VT exposure. To determine whether IL-5 or IL-6 play a role in IgA hyperelevation in vitro, PP and spleen cells from mice obtained 2 h after exposure to 25 mg/kg VT were cultured in the presence of neutralizing cytokine antibodies (Abs) and IgA production was monitored. Consistent with IL-5's previously documented role in IgA production, anti-IL-5 decreased IgA levels to background in cultures of both control and VT-exposed PP or spleen cells in the presence of either PMA + ION or LPS. Similar results were seen with addition of anti-IL-6. IgA levels were decreased to a lesser extent in PP cells cultured with LPS and in spleen cells cultured with PMA + ION from VT-exposed mice to which anti-IL-2 Ab was added. Thus, the potential for enhanced IgA production exists in lymphocytes as early as 2 h and as late as 24 h after a single oral exposure to VT and this may be related to the increased capacity to secrete helper cytokines of T cell and macrophage origin. Taken together, the results suggest that the superinduction of cytokine expression may, in part, be responsible for upregulation of IgA secretion in mice exposed orally to VT.
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PMID:Potential role for IL-5 and IL-6 in enhanced IgA secretion by Peyer's patch cells isolated from mice acutely exposed to vomitoxin. 927 10

Antibody isotype affects biological activity of the antibodies and therefore should be considered in prevention of disease by vaccination. In previous reports, we demonstrated that adjuvants affect the antibody isotype switching process and favour the production of certain isotypes. The present study extends these findings and shows fundamental differences in the cytokine induction pattern according to the adjuvant used. Cytokine mRNA levels were determined by in situ RNA-RNA hybridization performed on splenocytes isolated from mice injected with different adjuvants. The results revealed that Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), Al(OH)3 and QuilA administration results in a type-2 (humoral) response, increasing IL-4, IL-5 and IL-13 gene expression, while poly I:C exhibits a type-1 (cell-mediated) response, increasing the production of interferon-gamma (IFN-gamma), IL-2 and IL-6 mRNA. Finally, BeSO4 and poly A:U augment IL-5 and IL-6 mRNA production, while lipopolysaccharide (LPS) and LiCl augment IL-6 and tumour necrosis factor-alpha (TNF-alpha) mRNA production. Also, the adjuvants appear capable of overcoming the inherent IL-2/IFN-gamma and IL-4 dichotomy of C57B1/6 and BALB/c mice, respectively, in response to cellular antigens such as Leishmania and herpes simplex virus (HSV). The overall data suggest that adjuvants direct the isotype switching process via induction of certain cytokines, a finding that can be useful in selection of the most efficient isotype of protective antibodies for disease prevention by vaccination.
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PMID:Regulation of cytokine gene expression by adjuvants in vivo. 932 38

Bronchopulmonary hyperresponsiveness (BHR) is a hallmark of asthma and other inflammatory diseases of the airways. Animal models of BHR are available in which systemic or local immunizations, followed by acute allergenic provocations into the airways, augment responses to intravenous or intratracheal nonspecific bronchoconstrictor agents. Guinea-pig models are easy to manipulate but have serious handicaps: lack of proper genetics, lack of biomolecular tools, and frequent excess of eosinophils in the bronchoalveolar lavage fluid (BALF). Murine models have proper genetics and molecular tools, and they have the further advantage of being widely used for the study of other pathologies. In many of these studies, interleukin (IL)-5 appears as a major cytokine, produced by Th2 lymphocytes. Interleukin-5 promotes eosinophil differentiation and maturation, recruitment to the airways, and possibly activation. The presence of eosinophils in the airways and in the BALF may be necessary but is not sufficient to support BHR, since intense eosinophilia may be present in its absence. Bronchopulmonary hyperresponsiveness is also induced by the administration of lipopolysaccharide (LPS); in that case, eosinophils are not involved, and the role of neutrophils and of tumor necrosis factor-alpha, even though likely, has not been proven. Comparison of BHR induced by allergen (Th2- and largely eosinophil-dependent) and by LPS (probably macrophage-dependent) should allow for a better understanding of the mechanisms of BHR and for the development of important remedies.
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PMID:Modifications of experimental bronchopulmonary hyperresponsiveness. 935 87

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

When used in commercial fermented dairy products, bifidobacteria may enhance immunity by stimulating cytokine secretion by leukocytes. To assess whether interaction between bifidobacteria and leukocytes promote cytokine production, we cultured RAW 264.7 cells (macrophage model) and EL-4.IL-2 thymoma cells (helper T-cell model) in the presence of 14 representative strains of heat-killed bifidobacteria. In unstimulated RAW 264.7 cells, all bifidobacteria induced pronounced increases (up to several hundred-fold) in the production of tumor necrosis factor-alpha compared with that of controls. Interleukin-6 production by unstimulated cells also increased significantly, but less than did tumor necrosis factor-alpha. Upon concurrent stimulation of RAW 264.7 cells with lipopolysaccharide, production of tumor necrosis factor-alpha and interleukin-6 were both enhanced between 1.5- to 5.8-fold and 4.7- to 7.9-fold, respectively, when cultured with 10(8) bifidobacteria/ml. In unstimulated EL-4.IL-2 cells, bifidobacteria had no effect on the production of interleukin-2 or interleukin-5. Upon stimulation of EL-4.IL-2 with phorbol-12-myristate-13-acetate, there were variable increases in interleukin-2 secretion (up to 2.4-fold for 10(6) Bifidobacterium Bf-1/ml) and interleukin-5 secretion (up to 4.6-fold for 10(8) B. adolescentis M101-4). The results indicated that, even when variations among strains were considered, direct interaction of most bifidobacteria with macrophages enhanced cytokine production, but the effects on cytokine production by the T-cell model were less marked. Interestingly, the 4 bifidobacteria strains used commercially for diary foods showed the greatest capacity for cytokine stimulation. The in vitro approaches employed here should be useful in future characterization of the effects of bifidobacteria on gastrointestinal and systemic immunity.
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PMID:Differential cytokine production in clonal macrophage and T-cell lines cultured with bifidobacteria. 940 65

We have shown that bone marrow microvascular endothelial cells (BMEC) support growth and differentiation of haemopoietic progenitors in vitro by elaboration of haemopoietic cytokines. Since generation of eosinophils can be observed in these coculture experiments, and BMEC do not produce interleukin (IL)-3, we evaluated BMEC for expression of IL-5, a specific growth factor for the eosinophilic lineage. Using RT-PCR, IL-5 mRNA was expressed by BMEC after stimulation (12 h) with lipopolysaccharide (LPS), IL-1, IL-2 and phorbol myristate acetate (PMA), but not by resting BMEC, after stimulation with TNF-alpha or interferon (IFN)-gamma. Moreover, IFN-gamma suppressed expression of IL-5 in response to LPS and IL-2. The identity of the PCR products was confirmed by restriction enzyme digestion, which resulted in fragments of the predicted size. T lymphocytes were not present in the endothelial cultures as demonstrated by absence of CD2 mRNA. Using a sensitive (1 pg/ml) ELISA assay. IL-5 was detected after 48 h incubation of BMEC with IL-2 (4.1 pg/10(6) cells) or with a combination of LPS and IL-2 (4.8 pg). However, the number of eosinophils generated after 4 weeks coculture of CD34+ haemopoietic cells with BMEC was not increased by addition of IL-2. RT-PCR revealed that BMEC in coculture with haemopoietic cells expressed IL-5 even without addition of exogenous cytokines or stimulating agents. In conclusion, expression of IL-5 by BMEC can be stimulated by cytokines (IL-1, IL-2), LPS, PMA, and coculture with proliferating haemopoietic cells. Thus, BMEC may support proliferation and differentiation of eosinophils in the bone marrow. IFN-gamma represents a cytokine with an inhibitory effect on IL-5 expression by BMEC. In addition, eosinophilia in response to circulating IL-2 or bacterial products (LPS) in vivo may be partially mediated by BMEC or vascular endothelium.
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PMID:Expression of interleukin-5 by human bone marrow microvascular endothelial cells: implications for the regulation of eosinophilopoiesis in vivo. 943 15

We compared the abilities of different Salmonella enterica var. Typhimurium (S. typhimurium) strains harboring mutations in the genes aroA, aroAD, purA, ompR, htrA, and cya crp to present the heterologous antigen, C fragment of tetanus toxin, to the mouse immune system. Plasmid pTETtac4, encoding C fragment, was transferred into the various S. typhimurium mutants, and the levels of antigen expression were found to be equivalent. After primary oral immunization of BALB/c mice, all attenuated strains were capable of penetrating the gut epithelium and colonizing the Peyer's patches and spleens of mice. Of all strains compared, the delta purA mutant colonized and persisted in the Peyer's patches at the lowest level, whereas the delta htrA mutant colonized and persisted in the spleen at the lowest level. The level of specific antibody elicited by the different strains against either S. typhimurium lipopolysaccharide or tetanus toxoid was strain dependent and did not directly correlate to the mutants' ability to colonize the spleen. The level of immunoglobulin G1 (IgG1) and IgG2a antibody specific for tetanus toxoid was determined in mice immunized with four S. typhimurium mutants. The level of antigen-specific IgG1 and IgG2a was significantly lower in animals immunized with S. typhimurium delta purA. Antigen-specific T-cell proliferation assays indicated a degree of variability in the capacity of some strains to elicit T cells to the heterologous antigen. Cytokine profiles (gamma interferon and interleukin-5) revealed that the four S. typhimurium mutants tested induced a Th1-type immune response. Mice were challenged with a lethal dose of tetanus toxin 96 days after oral immunization. With the exception of the S. typhimurium delta purA mutant, all strains elicited a protective immune response. These data indicate that the level of total Ig specific for the carried antigen, C fragment, does not correlate with the relative invasiveness of the vector, but it is determined by the carrier mutation and the background of the S. typhimurium strain.
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PMID:Comparison of the abilities of different attenuated Salmonella typhimurium strains to elicit humoral immune responses against a heterologous antigen. 945 34

Polyclonal B-cell activation is the central theme in the production of autoantibodies and possible activation of autoreactive T cells in both human and murine lupus. The abnormal expansion of CD5+ B cells in murine lupus has been suggested, in particular, to be one of the most characteristic findings in these mice. Activated B cells can be separated from the B cells of resting stage by the difference in cell density. The aim of this study was to investigate the characteristics of different densities of the spleen cells separated by gradient density. Furthermore, the ability of anti-DNA antibody secretion in each percoll gradient fraction of B cells was also analysed. The results showed: a higher percentage of CD5+ B cells, which corresponded to the activated B-cell population, in percoll gradient 1 and 2 fractions; that splenic B cells of NZB/W F1 mice had proliferative response to interleukin (IL)-4 or IL-5 but not to IL-10 or interferon-gamma (IFN-gamma); and that B cells isolated by percoll gradient produced anti-DNA antibody after stimulation with lipopolysaccharide (LPS) plus IL-5 and IFN-gamma, but not IL-4 and IL-10. These data suggest that B cells at different stages of activation express differential characteristics and functions.
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PMID:Phenotypic and functional analysis of activated B cells of autoimmune NZB x NZW F1 mice. 949 86

The effects of four commercial strains of Streptococcus thermophilus used in yogurt manufacturing on cytokine production were evaluated by using a macrophage model (RAW 264.7 cells) and a T-helper-cell model (EL4.IL-2 thymoma cells) and compared to immunologically active strains of Lactobacillus bulgaricus, Bifidobacterium adolescentis, and Bifidobacterium bifidum. All cytokines (TNF-alpha and IL-6 in RAW 264.7 cells and IL-2 and IL-5 in EL4.IL-2 cells) were affected by heat-killed S. thermophilus in a strain- and dose-dependent fashion. Organisms of all three genera induced significant increases in IL-6 production by the macrophage line ranging from 31- to 192-fold, with S. thermophilus St 133 showing the greatest activity. The four S. thermophilus strains also strongly induced TNF-alpha production (from 135- to 176-fold). IL-6 and, to a lesser extent, TNF-alpha production were also increased when the macrophages were costimulated with lipopolysaccharide and cells of the three groups of lactic acid bacteria. Upon concurrent stimulation of EL4.IL-2 cells with phorbol 12-myristate-13-acetate, seven of the eight strains displayed significant enhancement of IL-2 and IL-5 production, with S. thermophilus being most effective. Taken together, the S. thermophilus strains stimulated macrophage and T-cell cytokine production to a similar or greater extent than did the species of Bifidobacterium and Lactobacillus. These and previous results lend further support to the contention that lactic acid bacteria, in a concentration-dependent manner, can differentially induce cytokine production in macrophages, but that the effects on T cells required a costimulatory signal and were less remarkable.
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PMID:Stimulation of cytokine production in clonal macrophage and T-cell models by Streptococcus thermophilus: comparison with Bifidobacterium sp. and Lactobacillus bulgaricus. 967 70

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