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 silicosis, alveolar macrophages (AM) are thought to induce chronic inflammation and fibrosis by release of cytokines. Rats were exposed to aerosols of alpha-quartz and examined 4 to 9 mo later for persistence of silica particles and release of tumor necrosis factor-alpha (TNF-alpha) from macrophages. Silica particles were detected in AM, lung parenchyma, and thoracic lymphoid organs, whereas extrathoracic lymphoid tissues and organs were free of the mineral. When AM were tested functionally, no spontaneous release of TNF-alpha was observed. However, upon in vitro stimulation of AM from silicotic rats with a low concentration of lipopolysaccharide (10 ng/ml), abundant TNF-alpha production was found that was higher and occurred more rapidly than with AM from sham-exposed animals. Peritoneal macrophages, which did not have contact with silica particles, displayed a similarly enhanced TNF-alpha release in response to low doses of lipopolysaccharide. These data demonstrate a state of systemic preactivation ("priming") of macrophages that supports the notion that silicosis is associated with a general immunostimulation.
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PMID:Systemic macrophage stimulation in rats with silicosis: enhanced release of tumor necrosis factor-alpha from alveolar and peritoneal macrophages. 191 Aug 24

The acute monocytic leukemia cell line, THP-1, is frequently used as a model to study the mechanism of cell-mediated immune response. The model is justified, in part, because THP-1 cells can be induced to express features of activated peripheral blood monocytes or tissue macrophages. The current investigation, however, demonstrates that THP-1 cells differ from normal monocytes in their secretion of interleukin-1 beta (IL-1 beta) following exposure to reagents that induce synthesis. For example, LPS treatment alone did not result in IL-1 beta secretion and very low concentrations were observed when lipopolysaccharide (LPS)-treated cells were simultaneously incubated with silica or silica in combination with hydroxyurea. Silica-enhanced release of IL-1 was related to changes in cell membrane permeability. Recombinant interferon-gamma (rIFN gamma) alone did not induce IL-1 beta secretion and did not significantly increase secretion by LPS- and silica-stimulated cells. In contrast, mezerein stimulation led to higher extracellular concentrations of IL-1 beta and rIFN gamma augmented secretion by mezerein-treated cells. Isoelectrofocusing of conditioned medium and titration of pooled fractions showed a direct correlation between extracellular levels of biologically active and immunoreactive IL-1. The role of IFN gamma in stimulating IL-1 beta secretion was not related to an enhancement of viability or an increase in the proportion of mezerein-treated cells synthesizing DNA. It was concluded that mezerein's regulation of secretion by THP-1 cells depended on the expression of monocyte features, including cell adherence and responsiveness to IFN gamma.
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PMID:Secretion of interleukin-1 beta by a leukemia cell line in response to lipopolysaccharide and mezerein. 211 75

Antibacterial agents which specifically inhibit CTP:CMP-3-deoxy-D-manno-octulosonate cytidylyltransferase activity were used to block the incorporation of 3-deoxy-D-manno-octulosonate (KDO) into lipopolysaccharide. Lipopolysaccharide synthesis ceased, molecules similar in structure to lipid A accumulated, and bacterial growth ceased following addition of such agents to cultures of Salmonella typhimurium and Escherichia coli. Although four major species of lipid A accumulated in S. typhimurium, their kinetics of accumulation were different. The least polar of the major species was IVA [O-(2-amino-2-deoxy-beta-D-glucopyranosyl)-(1----6)-2-amino-2-deoxy-a lph a- D-glucose, acylated at positions 2, 3, 2', and 3' with beta-hydroxymyristoyl groups and bearing phosphates at positions 1 and 4'], a molecule previously isolated from bacteria containing a kdsA mutation (C. R. H. Raetz, S. Purcell, M. V. Meyer, N. Qureshi, and K. Takayama, J. Biol. Chem. 260:16080-16088, 1985). Species IVA accumulated first and to the greatest extent following addition of the inhibitor, with other more polar derivatives appearing only after IVA attained half its maximal level. In contrast, only two major species of precursor accumulated in E. coli following addition of the inhibitor. One of these species was identical to IVA from S. typhimurium on the basis of chemical composition, fast atom bombardment mass spectroscopy, and comigration on Silica Gel H, and it also accumulated prior to a more polar species of related structure. We conclude that the addition of KDO to precursor species IVA is the major pathway of lipid A-KDO formation in both S. typhimurium LT2 and E. coli and that accumulation of the more polar species lacking KDO only occurs in response to accumulation of species IVA following inhibition of the normal pathway.
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PMID:Analysis of lipopolysaccharide biosynthesis in Salmonella typhimurium and Escherichia coli by using agents which specifically block incorporation of 3-deoxy-D-manno-octulosonate. 283 31

Silica has been used for many years as an agent which selectively alters macrophage functions and, as such, has been used to assess the role of macrophages in the immune response to a variety of microbial and chemically defined agents. Silica treatment of C3H/HeN mice 1 day before challenge with protein-free Escherichia coli endotoxin (lipopolysaccharide [LPS]) resulted in a marked increase in LPS sensitivity, as evidenced by accelerated signs of endotoxemia as well as a fourfold decrease in the LPS 50% lethal dose. The silica-mediated increase in responsiveness to LPS was associated with increased production of macrophage-derived soluble factors both in vivo (interferon) and in vitro (Interleukin 1; previously referred to as lymphocyte activating factor or LAF) upon endotoxin stimulation. These findings support the central role of the macrophage and its products in mediating endotoxic reactions.
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PMID:Silica enhancement of murine endotoxin sensitivity. 618 19

The role of macrophages in the innate immunity of mice to histoplasmosis was investigated using silica, which selectively inactivates macrophages. Mice given silica IV 1 day prior to challenge with live yeast cells of Histoplasma capsulatum were more susceptible to infection than were untreated controls. This increased susceptibility to Histoplasma was observed when mice were given silica at 1, 14, and 21 days prior to infection but not at 3 and 7 days. Silica treated mice that survived 30 days after challenge with a sublethal dose of Histoplasma had 23 times more viable organisms in their spleens than in those of untreated controls. The blastogenic response of spleen cells to concanavalin A and phytohemagglutinin was unaffected at 12 hr after silica injection but was significantly depressed between 1 and 21 days. In contrast, silica treatment did not affect the blastogenic response of spleen cells to lipopolysaccharide. Silica particles were cytotoxic for mouse peritoneal macrophages but not to lymphocytes in vitro. These results indicate that macrophages play an essential role in natural immunity to histoplasmosis.
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PMID:Effect of silica on the susceptibility of mice to experimental histoplasmosis. 631 Jan 9

Macrophages play a key role in natural host defense against infection by a variety of pathogens. In addition, macrophages initiate the development of acquired immunity via antigen processing and presentation. The role of macrophages in resistance to pathogens, the development of autoimmune diseases and the induction of acquired immunity has been studied by treatment of rodents with reagents which are cytotoxic. We have studied the effects of one such reagent, silica, on the function of spleen macrophages and peritoneal exudate cells (PEC). Intraperitoneal administration of silica caused the accumulation of spleen macrophages and neutrophils, reduction in the number of B cells and had a modest effect on T cell abundance. The percentage of CD11b+ PEC was not affected by silica treatment but total PEC recovery was diminished 5-8 fold. Silica treatment did not cause release of TNF-alpha or IL-1-beta but, when stimulated with lipopolysaccharide (LPS) in vitro after silica treatment, PEC or spleen macrophages produced elevated levels of both cytokines compared to controls. In contrast, release of IL-12 from non-LPS treated PEC was stimulated 4-5 fold by silica treatment. In addition, sensitivity to LPS toxicity in vivo was significantly enhanced by silica. The ability of macrophages to present antigen to a T cell clone in vitro was found to be dramatically inhibited by silica treatment, as was the ability to prime antigen-specific T cells and B cells by antigen injection. Collectively these data demonstrate that silica treatment enhances macrophage sensitivity to LPS exposure but inhibits antigen processing and presentation.
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PMID:Administration of silica sensitizes lipopolysaccharide responsiveness of murine macrophages but inhibits T and B cell priming by inhibition of antigen presenting function. 965 66

Basal, lipopolysaccharide (LPS) and silica-stimulated prostaglandin (PG) production were compared between peripheral blood mononuclear cells (PBMNC) from UC patients and healthy subjects (HS). Basal and LPS-stimulated PBMNC PGI2, but not PGE2, production was greater in UC. LPS stimulated both PGE2 and PGI2 by PBMNC from HS and UC patients. Silica stimulated production of both PGs by cells from HS but only PGE2 by cells from UC patients. The differences in responses to silica and LPS may result from differences in activation of NFkappaB or, alternatively, prior sensitisation to one of these agents. That PBMNC PGE2 production is not increased in UC, as it is in Crohn's disease, suggests that there are differences in PBMNC behaviour between these two diseases.
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PMID:Lipopolysaccharide and silica-stimulated mononuclear cell prostaglandin production in ulcerative colitis. 1113 77

Alveolar macrophages play a critical role in silica-induced lung fibrosis. Silica exposure induces tumor necrosis factor (TNF)-alpha release and nuclear factor (NF)-kappaB activation, and apoptotic mechanisms have been implicated in silica-induced pathogenesis. To characterize potential relationships between these signaling events, we studied their induction in two murine macrophage cell lines. The RAW 264.7 macrophage cell line was more sensitive, and the IC-21 macrophage cell line more tolerant to silica exposure (0.2 or 1 mg/ml for 6 h) as evidenced by significantly higher apoptotic responses in RAW 264.7 (P < 0.05). RAW 264.7 macrophages exhibited enhanced TNF-alpha production and NF-kappaB activation in response to silica, whereas IC-21 macrophages did not produce TNF-alpha in response to silica and did not induce NF-kappaB nuclear binding. Inhibition of NF-kappaB in RAW 264.7 cells with BAY11-7082 significantly increased apoptosis while inhibiting TNF-alpha release. In addition, TNF-alpha and NF-kappaB activation, but not apoptosis, were induced by lipopolysaccharide (LPS) in both cell lines, and NF-kappaB inhibition reduced LPS-induced TNF-alpha release. These data suggest that TNF-alpha induction is dependent on NF-kappaB activation in both cell lines. However, silica can induce apoptosis in murine macrophages, independently of TNF-alpha stimulation, as in IC-21 macrophages. Furthermore, NF-kappaB activation in macrophages may play dual roles, both pro- and antiapoptotic during silica injury.
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PMID:Silica-induced apoptosis in murine macrophage: involvement of tumor necrosis factor-alpha and nuclear factor-kappaB activation. 1209 Dec 51

Bioactive materials have previously been used to coat implants. In a new development for bioactive materials, a silica-ceramic mixture was found to alleviate pain (Lee, Poster presented at the Ninth World Congress of Gynecological Endocrinology, Hongkong, 2001. Poster session (p47)). Here, we hypothesized that silica-ceramic can reduce the expression and activity of cyclooxygenase 2 (COX2) or cytokines associated with inflammation. The production of COX2 and proinflammatory cytokines was investigated by reverse transcriptase (RT)-PCR and ELISA assay in macrophages stimulated by lipopolysaccharide (LPS). Silica-ceramic had no effect of COX2 expression and prostaglandin production in macrophages. However, silica-ceramic suppressed the synthesis of cytokines involved in inflammation, in particular, the expression of IL-1beta and IL-6 was reduced at the transcriptional and translational levels. The involvement of NF-kappaB in the suppression of cytokines by silica-ceramic was examined by luciferase reporter assay. The NF-kappaB activity stimulated by LPS was inhibited by 20-60% with silica-ceramic compared with treatment with LPS alone. We suggest that inhibition of NF-kappaB activity by silica-ceramic might cause the attenuation of proinflammatory cytokine expression in macrophages. In conclusion, silica-ceramic could be an alternative approach to regulate the inflammation process.
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PMID:Silica-ceramic suppresses the expression of proinflammatory cytokines induced by lipopolysaccharide in macrophages. 1713 51

Inhalation of silica, without evidence of silicosis, is believed to predispose individuals to bacterial infections and impair respiratory immune functions. Silica may alter the sensitivity of antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs), to other types of infection; however, the exact nature of these exchanges remains uncertain. The purpose of the present study is to characterize the effect of silica exposure on innate pulmonary defense mechanisms following Toll-like receptor (TLR) ligand-induced activation using DCs as a model APC and determine whether these signals act in synergy or opposition to one another. Using C57Bl/6 mice, pattern recognition receptor expression on DCs was examined in vitro and in vivo using flow cytometry, and the activation state of pulmonary and granulocyte-macrophage colony-stimulating factor-derived DCs was assessed in response to silica in combination with TLR ligands (lipopolysaccharide, cytosine-phosphate-guanine, or polyinosinic:polycytidylic acid) using flow cytometry and measurement of cytokine production. In this study, silica attenuated TLR ligand-dependent DC activation with regards to accessory molecule expression as well as nitric oxide and inflammatory cytokine production. Furthermore, silica's ability to modulate TLR ligand-dependent DC activation did not appear to be dependent on the class A scavenger receptors. Taken together, silica's ability to alter susceptibility to infection may be due to impaired inflammatory responses and reduced antibacterial activity.
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PMID:Silica suppresses Toll-like receptor ligand-induced dendritic cell activation. 1818 Mar 31


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