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)

Capsaicin stimulates cyclic GMP production via nitric oxide (NO) (or another nitrosyl factor) in dorsal root ganglion (DRG) neurons maintained in culture. The purpose of the present study was to characterize further capsaicin stimulation of cyclic GMP production in DRG cells maintained in culture, investigate other algesic and/or inflammatory agents for effects on cyclic GMP production, and examine cells responsible for NO production and cyclic GMP production. Capsaicin stimulation of cyclic GMP production in DRG cells was dose dependent, receptor mediated, and attenuated by hemoglobin. Prostaglandin E2, substance P, and calcitonin gene-related peptide did not affect basal, capsaicin-stimulated, or bradykinin-stimulated cyclic GMP production. Other inflammatory or algesic agents, including serotonin, histamine, ATP, glutamate, aspartate, and NMDA, did not affect cyclic GMP production. Pretreatment of DRG cells with lipopolysaccharide increased basal cyclic GMP production in neuronal but not in nonneuronal cultures and facilitated stimulation of cyclic GMP production by L-arginine. Capsaicin pretreatment of neuronal DRG cultures, which destroys capsaicin-sensitive (small diameter) afferent neurons, attenuated capsaicin- and bradykinin-stimulated cyclic GMP production but did not affect basal or sodium nitroprusside-stimulated cyclic GMP production. These results indicate that capsaicin elicits production of a nitrosyl factor via capsaicin-sensitive (small diameter) neurons. Capsaicin evoked cyclic GMP production in nonneuronal DRG cultures in the presence but not in the absence of apposed neuronal DRG cultures. Overall, these findings suggest that specific exogenous (or endogenous) substances may stimulate production of a nitrosyl factor(s) by a subset of DRG neurons, and nitrosyl factors produced by these neurons may affect cyclic GMP production in neighboring neuronal or non-neuronal cells.
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PMID:Stimulation of cyclic GMP production via a nitrosyl factor in sensory neuronal cultures by algesic or inflammatory agents. 779 Aug 81

Kupffer cells are the largest population of fixed tissue macrophages in the body and produce a number of mediators that are involved in host defense. These mediators include cytokines such as tumor necrosis factor-alpha and interleukin-1, prostaglandins, oxygen radicals, and nitric oxide. Prostaglandins are produced by adjacent endothelial cells in addition to Kupffer cells and regulate a number of cellular functions in a wide array of cells, but their role in nitric oxide synthesis is controversial. We studied the role of prostaglandins in regulating lipopolysaccharide (LPS)-induced nitric oxide synthesis in cultured rat Kupffer cells. Prostaglandin E2 (PGE2) inhibited Kupffer cell nitric oxide synthesis in a dose-dependent fashion in both 24- and 48-hr cultures. The effect of PGE2 persisted at low and high LPS concentrations. Prostaglandin analogues as well as other prostanoids also inhibited Kupffer cell nitric oxide synthesis. These data show that exogenous prostaglandins suppress Kupffer cell nitric oxide synthesis and may represent an important endogenous regulator of nitric oxide production.
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PMID:Prostanoids inhibit Kupffer cell nitric oxide synthesis. 779 38

Prostaglandin E2 (PGE2) is generally accepted to be a negative feedback effector of tumor necrosis factor alpha (TNF alpha) production. However, we have observed that a cyclooxygenase inhibitor had different effects on TNF alpha production by resident and thioglycollate-elicited rat peritoneal macrophages. Indomethacin coordinately reduced PGE2 production and increased TNF alpha production in lipopolysaccharide (LPS)-stimulated resident macrophages, whereas indomethacin reduced PGE2 production without affecting TNF alpha production in thioglycollate-elicited macrophages. PGE2 production and arachidonate release were much less in thioglycollate-elicited macrophages than in resident macrophages. However, exogenously added PGE2 suppressed TNF alpha production to the same extent in the two macrophage populations. The addition of free arachidonic acid to cultures of LPS-stimulated, thioglycollate-elicited macrophages elevated PGE2 production and suppressed TNF alpha production in a manner similar to that observed with LPS-stimulated resident macrophages. These results indicate that the differential effects of indomethacin treatment on TNF alpha production observed between the two macrophage populations are not due to the differences in arachidonate contents, PGE2 productivities, nor to their capacities to respond to PGE2. Instead, the inability of indomethacin to increase TNF alpha production by thioglycollate-elicited versus resident macrophages appears to result from an inability to release arachidonate efficiently and a lower initial level of cyclooxygenase, in thioglycollate-elicited macrophages.
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PMID:Regulation of lipopolysaccharide-induced tumor necrosis factor alpha production by endogenous prostaglandin E2 in rat resident and thioglycollate-elicited macrophages. 781 78

Interleukin-6 has a variety of biological effects, mainly on the immune system. The regulation of this signal at both the site of production and the site of action is necessary to maintain the organism's homeostasis. In the microenvironment of the hepatic sinusoids, Kupffer cells as resident macrophages are the most potent source of interleukin-6 during inflammation. This cytokine is an important signal to hepatocytes during the early stages of the acute-phase response, leading to the expression of several major plasma proteins. Kupffer cells were found to express interleukin-6 receptor constitutively. Interleukin-6 decreased the level of interleukin-6 receptor mRNA, indicating an autocrine pathway by which Kupffer cells regulate their responsiveness to interleukin-6. Furthermore, lipopolysaccharide, tumor necrosis factor-alpha, interferon-gamma, interleukin-1 beta and phorbol ester induced interleukin-6 production and, at the same time, suppressed the level of interleukin-6 receptor mRNA. The existence of an autocrine loop in rat Kupffer cells may be physiologically relevant, as it would contribute to a regulated interleukin-6 signal chain in the liver. The anti-inflammatory mediators dexamethasone or PGE2 and its second messenger, cyclic AMP, increased interleukin-6 receptor mRNA, whereas prostaglandin D2 or the Ca2+ ionophore, A 23187, were without effect. The changes in interleukin-6 mRNA were paralleled by the number of interleukin-6 receptors present on Kupffer cells as detected by binding of 125I-interleukin-6. These results suggest the existence of control mechanisms involving several soluble mediators that help balance the level of interleukin-6-R mRNA in rat liver macrophages.
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PMID:Regulation of interleukin-6 receptor expression in rat Kupffer cells: modulation by cytokines, dexamethasone and prostaglandin E2. 781

The use of smokeless tobacco (ST) products is associated with mucosal lesions, gingival recession, and attachment loss at the site of tobacco placement. Monocytes/macrophages are primary producers of PGE2 and IL-1 beta, inflammatory mediators which are thought to play a role in the destruction of the periodontium. The purpose of this study was to determine the effect of ST alone and in combination with a major stimulator of inflammation, bacterial lipopolysaccharide (LPS), on monocyte secretion of these mediators. Peripheral blood monocytes (PBM) were isolated by counterflow centrifugal elutriation from 15 healthy donors who were non-ST users. PBM were incubated for 24 hours in RPMI 1640 containing various concentrations of ST (0%, 0.005%, 0.01%, 1%) with or without 10 micrograms/ml LPS (Porphyromonas gingivalis LPS or Escherichia coli LPS). Of the ST preparations, only 1% ST resulted in PBM mediator secretion (7.7 +/- 2.0 ng/ml for PGE2 and 1.3 +/- 0.2 ng/ml for IL-1 beta) above that of control (unstimulated) cultures. Furthermore, the combination of 1% ST and LPS resulted in a potentiation of PGE2 release (5-fold for E. coli LPS + 1% ST and 10-fold for P. gingivalis LPS + 1% ST; P < 0.0001, one-way ANOVA) relative to the LPS preparations alone. In contrast, PBM IL-1 beta release decreased more than 2-fold upon E. coli LPS and 1% ST exposure, relative to treatment with E. coli LPS alone (P < 0.0001, one-way ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Smokeless tobacco effects on monocyte secretion of PGE2 and IL-1 beta. 782 75

The effect of a novel liposomal preparation containing a phospholipid conjugate of methotrexate (MTX-LIPO) upon macrophage mediator release was investigated in normal and arthritic rats ex vivo. Peritoneal macrophages isolated from MTX-LIPO-treated arthritic rats and stimulated with lipopolysaccharide produced significantly less tumor necrosis factor (TNF) and prostaglandin (PGE2) than did macrophages isolated from saline-treated controls. In the same experimental system, free methotrexate only inhibited prostaglandin release, but it was more potent than MTX-LIPO in this respect. Additional studies are presently underway to investigate the effect of MTX-LIPO and MTX treatment upon the lipopolysaccharide-induced rise in plasma levels of various proinflammatory mediators in vivo. Haematopoietic toxicity was demonstrated in blood isolated from rats treated with free MTX, and this was as characterized by a significant reduction in reticulocyte count compared with MTX-LIPO and saline-treated rats.
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PMID:Prostaglandin and tumor necrosis factor secretion by peritoneal macrophages isolated from normal and arthritic rats treated with liposomal methotrexate. 783 8

Endotoxin [lipopolysaccharide (LPS) 50 micrograms/mL] added to the perfusion medium increased glucose production and inhibited the glucuronidation of p-nitrophenol in perfused mouse liver both in recirculating and non-recirculating systems, while sulfation of p-nitrophenol was unchanged. The effects of endotoxin could be prevented by the addition of cyclooxygenase inhibitors, while PGD2 and PGE2 also caused a decrease in p-nitrophenol glucuronidation in perfused liver. In isolated hepatocytes endotoxin failed to affect p-nitrophenol conjugation, while PGD2 and PGE2 decreased the rate of it. Our results suggest that endotoxin inhibits glucuronidation through an intercellular communication presumably mediated by eicosanoids.
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PMID:Endotoxin inhibits glucuronidation in the liver. An effect mediated by intercellular communication. 784 Jul 84

Metabolites of arachidonic acid have been shown to be potent biological modulators of macrophage function. While the role of cyclooxygenase metabolites of arachidonic acid have been well studied, metabolites of lipoxygenase have not. In this report, we evaluate the role that select 5'-lipoxygenase (5'-LO) products may play in macrophage activation for select tumoricidal functions. When thioglycollate-elicited macrophages were treated with inhibitors of 5'-LO during activation, cytolytic capacity, nitric oxide production, and tumor necrosis factor-alpha production were significantly inhibited. Moreover, both an inhibitor of the 5'-LO-activating protein and an inhibitor of glutathione-s-transferase (GST) significantly decreased macrophage tumoricidal function. The activating agents used were able to stimulate 5'-LO activity which was measured by quantitating secreted LTC4. Increased production of PGE2 by shunting could have been the cause for decreased macrophage tumoricidal function. However, treatment of macrophages with inhibitors of 5'-LO during lipopolysaccharide stimulation did not increase formation of PGE2. When select 5'-LO metabolites were added to cultures during activation and 5'-LO inhibition, tumoricidal activity could not be restored, even when the metabolites were encapsulated in liposomes. These results suggest that the activity of 5'-LO and GST are important for macrophage activation. However, the specific role of 5'-LO metabolites has not been completely established.
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PMID:Role of 5'-lipoxygenase metabolites in the activation of peritoneal macrophages for tumoricidal function. 784 77

1. Cyclo-oxygenase metabolizes arachidonic acid to prostaglandin H2 (PGH2) and exists in at least two isoforms. Cyclo-oxygenase-1 (COX-1) is expressed constitutively whereas COX-2 is induced by lipopolysaccharide (LPS) and some cytokines in vitro and at the site of inflammation in vivo. Epithelial cells may be an important source of prostaglandins in the airways and we have, therefore, investigated the expression of COX-1 or COX-2 isoforms in primary cultures of human airway epithelial cells or in a human pulmonary epithelial cell line (A549). 2. COX-1 or COX-2 protein was measured by western blot analysis using specific antibodies to COX-2 and selective antibodies to COX-1. The activity of COX was assessed by the conversion of either endogenous or exogenous arachidonic acid to four metabolites, PGE2, PGF2 alpha, thromboxane B2 or 6-oxo PGF1 alpha measured by radioimmunoassay. Thus, COX-1 or COX-2 activity was measured under two conditions; initially the accumulation of the COX metabolites formed from endogenous arachidonic acid was measured after 24 h. In other experiments designed to measure COX activity directly, cells were treated with cytokines for 12h before fresh culture medium was added containing exogenous arachidonic acid (30 microM) for 15 min after which COX metabolites were measured. 3. Untreated primary cells or A549 cells contained low amounts of COX-1 or COX-2 protein. Bacterial LPS (1 micro g ml-1 for 24 h) induced COX-2 protein in the primary cells, a process which was enhanced by interferon-gamma, with no further increase in the presence of a mixture of cytokines (interleukin-1 beta, tumour necrosis factor-alpha and interferon-gamma, 10 ng ml-1 for all). In contrast, A549 cells contained only low levels of COX-2 protein after exposure to LPS or LPS plus interferon-y, but contained large amounts of COX-2 protein after exposure to the mixture of cytokines.4. Untreated human pulmonary primary cells or A549 cells released low levels of all COX metabolites measured over a 24 h incubation period. This release was enhanced by treatment of either cell type with the mixture of cytokines (interleukin-1 beta , tumour necrosis factors- and interferon-gamma, 10 ng ml-1 for all).PGE2 was the principal COX metabolite released by cytokine-activated epithelial cells. The release of PGE2 induced by cytokines occurred after a lag period of more than 6 h.5. The glucocorticosteroid, dexamethasone (1 micro M; 30 min prior to cytokines) completely suppressed the cytokine-induced expression of COX-2 protein and activity in both primary cells and A549 cells.6. In experiments where COX-2 activity was supported by endogenous stores of arachidonic acid,treatment of A549 cells with interleukin-l beta but not tumour necrosis factor a or interferon-gamma alone caused a similar release of PGE 2 to that seen when the cytokines were given in combination. However, both interleukin-l beta and necrosis factor- alone produced similar increases in COX-2 activity (measured in the presence of exogenous arachidonic acid) as seen when the mixture of interleukin-l beta, tumour necrosis factor- alpha and interferon-gamma were used to stimulate the cells.7. These findings show that COX-2 expression correlates with the exaggerated release of prostaglandins from cytokine-activated human pulmonary epithelial cells and that the induction of the enzyme is suppressed by a glucocorticosteroid. These findings may be relevant to inflammatory diseases of the lung, such as asthma.
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PMID:Induction of cyclo-oxygenase-2 by cytokines in human pulmonary epithelial cells: regulation by dexamethasone. 785 42

Rat prostaglandin endoperoxidase synthase-2 (PGHS-2) cDNA was cloned from rat calvarial osteoblasts total RNA by RT-PCR. The primary sequence of rat PGHS-2 had 98% and 92% identity to the mouse and human enzymes, respectively. Transfection of the rat PGHS-2 cDNA into COS 7 cells, followed by the addition of 20 microM arachidonic acid, resulted in a dramatic increase in PGE2 released from these cells. The amount of PGE2 produced was comparable to that obtained from cells similarly transfected with human PGHS-1 cDNA. In the rat paw carrageenin-oedema inflammatory model, the injected paw had elevated levels of PGHS-2 mRNA compared to the control paw. In a rat pyrexia model, injection of the pyrogen lipopolysaccharide, resulted in elevated levels of PGHS-2 mRNA in the brain. These results suggest that PGHS-2 expression plays a role both in inflammation and fever.
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PMID:Cloning and expression of rat prostaglandin endoperoxide synthase (cyclooxygenase)-2 cDNA. 791 14


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