Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrite (NO2-) is the major end product of nitric oxide (NO) production in cell culture. The authors have examined nitrite production by glomeruli in in situ immune complex glomerulonephritis in the rat. Glomerulonephritis was induced by unilateral renal perfusion of cationized human gamma G immunoglobulin (IgG) in preimmunized rats. NO2- was measured in culture supernatants of isolated glomeruli after 48 hours. NO2- was produced by nephritic glomeruli with a maximum 4 days after induction of glomerulonephritis (24.4 +/- 11.4 pmol/glomerulus/48 hours). Production was increased by lipopolysaccharide (LPS; 1 micrograms/ml) (54 +/- 4.9 pmol/glomerulus; P less than 0.001). NO2- production was inhibited by the nitric oxide synthase inhibitor NG-monomethyl-L-arginine demonstrating synthesis through NO. Dexamethasone (10(-7) mol/l [molar]) reduced LPS-stimulated production by peritoneal macrophages and nephritic glomeruli (P less than 0.01). Macrophages isolated from nephritic glomeruli produced NO2- (4.9 +/- 0.6 nmols/10(5) cells). The production of NO by nephritic glomeruli has implications for mechanisms of glomerular injury and glomerular hemodynamics. The effect of dexamethasone may explain in part the ameliorative effect of steroids in glomerulonephritis.
 ...
PMID:Glomerular nitrite synthesis in in situ immune complex glomerulonephritis in the rat. 195 26

Bacterial lipopolysaccharide (LPS) exerts profound effects on mammalian hosts in part by inducing macrophages to release tumor necrosis factor-alpha (TNF-alpha); the mechanisms involved are unresolved. The microtubule stabilizer taxol shared two actions of LPS on macrophages: it rapidly decreased TNF-alpha receptors and triggered TNF-alpha release. Both actions of taxol were absent in LPS-hyporesponsive C3H/HeJ mice. In recombinant inbred mice, the genes controlling responses to LPS and to taxol were closely linked. Dexamethasone blocked release of TNF-alpha by both stimuli but did not block the decrease in TNF-alpha receptors. Thus, a protein associated with microtubules may be a cellular target of LPS.
 ...
PMID:Shared actions of endotoxin and taxol on TNF receptors and TNF release. 197 Jan 96

A pulmonary macrophage-monocyte-derived mucus secretagogue (MMS) oligopeptide has been previously reported to induce mucus secretion in an in vitro model system with human airway explants and secretory epithelial cells. To understand the possible role of macrophages in the regulation of secretion of mucus, our laboratory has used a series of human macrophage hybridomas that were generated by fusing an hypoxanthine guanine phosphoribosyl transferase-deficient promonocytic line, U937, with macrophages obtaining by maturing monocytes in Teflon bags. The cell lines were proven to be true hybridomas by acquisition of donor class I antigens, additional chromosomes, as well as macrophage specific (maximum velocity) not present on the U937 parent line. One clone, clone 63, produced large amounts of an oligopeptide with an approximate molecular weight of 2000, which was identified from culture supernatants by ultrafiltration, chromatography, isoelectric focusing, and Western blot. Processed clone 63 supernatant had biologic activity causing increased secretion of radiolabeled glycoconjugate in both cultured airways and secretory epithelial cells. Immunoblot analysis with a polyclonal rabbit antisera generated against MMS was positive, and Western blot analysis produced a band at approximately 2000 daltons, consistent with the previously described MMS. MMS secretion could be stimulated by zymosan and lipopolysaccharide and inhibited by both cycloheximide and erythromycin. Dexamethasone had a different effect, appearing to stimulate MMS production intracellularly but inhibiting its release once it was synthesized. The availability of cloned hybridomas allows for study of the regulation of mucus secretagogue production as well as purification of molecular species and provides a valuable tool for the study of mucus secretion.
 ...
PMID:Mucus secretagogue production by a human macrophage hybridoma. 199 9

A dose-dependent neutrophil migration was observed following the injection of purified (Hu IFN-gamma) or recombinant (rIFN-gamma) human gamma interferon into rat peritoneal cavities. This finding contrasts with their inability to cause chemotaxis in vitro in the Boyden chamber. Neutrophil migration into peritoneal cavities and subcutaneous air pouches induced by both preparations of interferon was abolished by pretreatment of the animals with dexamethasone. IFN-gamma-induced neutrophil migration was enhanced when the macrophage population of the peritoneal cavities was increased by previous injection of thioglycollate and reduced by peritoneal lavage. Macrophage monolayers pretreated either with rIFN-gamma or with lipopolysaccharide from E. coli release into the supernatant a factor that stimulates neutrophil recruitment in animals treated with dexamethasone. Dexamethasone blocked this release but did not affect the neutrophil recruitment induced by this factor. These results suggest that IFN-gamma-induced neutrophil migration in vivo may be mediated by the release from resident macrophages of a neutrophil chemotactic factor and that dexamethasone blockade of neutrophil recruitment by IFN-gamma is due to inhibition of the release of this factor.
 ...
PMID:Recombinant gamma interferon causes neutrophil migration mediated by the release of a macrophage neutrophil chemotactic factor. 211 90

We report here that the bacterial lipopolysaccharide endotoxin induces human blood monocytes in a time- and dose-dependent manner to release prodigious amounts of prostaglandins with thromboxane A2, the major metabolite formed. Cells responded to as little as 1 ng/ml lipopolysaccharide to release prostaglandin E2 and thromboxane A2 with maximal stimulation at 10 micrograms/ml. Lipopolysaccharide was found to induce increased activity of cyclooxygenase enzyme without affecting the activities of phospholipase and thromboxane synthase or the formation of 5-lipoxygenase products (e.g. leukotriene B4). The glucocorticoid dexamethasone completely blocked the lipopolysaccharide-induced prostanoid release by inhibiting the activity of monocyte cyclooxygenase. Dexamethasone did not affect phospholipase and thromboxane synthase activities or leukotriene formation. Immunoprecipitation of [35S]methionine-labeled cyclooxygenase confirmed that the effect of lipopolysaccharide and dexamethasone on the monocyte prostanoid production could be attributed to an increase or decrease, respectively, in cellular cyclooxygenase de novo synthesis.
 ...
PMID:The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. 212 Feb 5

The multipotential cytokine, transforming growth factor-beta 2 (TGF-beta 2), is as effective as glucocorticoids in suppressing the production of tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated macrophages, and this inhibition can be abrogated by exogenous interferon-gamma (IFN-gamma). Porcine alveolar macrophages triggered with LPS produce TNF-alpha as identified by complete blocking of cytotoxicity on WEHI 164 clone 13 cells in macrophage supernatants by a monoclonal antibody to human TNF-alpha. Platelet-derived porcine TGF-beta 2, at a concentration of 4 nM, inhibited LPS-induced production of TNF-alpha by 93%. Dexamethasone was as effective as TGF-beta 2, suppressing TNF-alpha production by 86% at a concentration of 4 nM. The natural but less potent glucocorticoid cortisol inhibited TNF-alpha production by 100% at a 100-fold higher concentration (400 nM). Recombinant PoIFN-gamma consistently primed LPS-triggered macrophages for increased production of TNF-alpha by 50-100%, and this priming was totally blocked by a polyclonal antibody to rPoIFN-gamma. Furthermore, the suppression in LPS-induced production of TNF-alpha caused by TGF-beta 2, dexamethasone, and cortisol could be reversed by addition of rPoIFN-gamma. These data show that alveolar macrophages can be effectively primed by rPoIFN-gamma even in the presence of moderately suppressive doses of TGF-beta 2 and antiinflammatory steroids.
 ...
PMID:Role of interferon-gamma in counteracting the suppressive effects of transforming growth factor-beta 2 and glucocorticoids on the production of tumor necrosis factor-alpha. 212 84

Tumor necrosis factor alpha (TNF alpha) mRNA is present in a preformed intracellular pool in the spleen, liver, and small bowel of naive rats. Endotoxin (Salmonella typhus lipopolysaccharide) injected intravenously induces little or no increase in whole-organ TNF mRNA levels at 15', 30', 1 degree, 2 degrees, or 4 degrees, whereas serum TNF levels are markedly elevated at 1 and 2 hours. Dexamethasone pretreatment of rats suppresses LPS-induced serum TNF concentrations, but does not suppress TNF mRNA levels in the spleen or bowel. Tachyphylaxis experiments demonstrate that a second injection of endotoxin 2 hours after an initial injection fails to induce a second peak of serum TNF, although TNF mRNA levels in the spleen and bowel remain at the levels found in naive rats. Corynebacterium parvum upregulates endotoxin-induced serum TNF release and intravenous injection of IL-1 induces the release of serum TNF but neither alters whole-organ TNF mRNA levels. Interleukin-1 alpha (IL-1 alpha) mRNA was not constitutively detected in whole-organ RNA preparations of the spleen, liver, and small bowel of naive rats. Endotoxin induces IL-1 alpha mRNA most easily appreciated in the spleen beginning at 1 hour, peaking at 2 to 4 hours, and disappearing by 6 hours. Interleukin-1 beta (IL-1 beta) mRNA was not constitutively detected in the organs examined or was present in small amounts. Endotoxin induces IL-1 beta mRNA beginning at 0.5 hours, peaking at 1 hour, and disappearing by 6 hours. Dexamethasone pretreatment prevents the LPS-induced appearance of IL-1 alpha mRNA and suppresses but does not completely inhibit the appearance of IL-1 beta mRNA. C. parvum upregulates endotoxin-induced IL-1 mRNA expression. Intravenous injection of TNF or IL-1 both induce IL-1 mRNA expression. In conclusion, TNF mRNA is constitutively expressed and TNF mRNA levels as analyzed in whole-organ RNA preparations do not change in concert with serum TNF protein levels during conditions of endotoxemia, dexamethasone treatment, tachyphylaxis, priming with C. parvum, or after injection of IL-1. In contrast, IL-1 mRNA expression during endotoxemia, dexamethasone treatment, priming with C. parvum, or after injection of TNF or IL-1 shows clear increases and decreases in whole-organ RNA preparations.
 ...
PMID:Endotoxin-induced cytokine gene expression in vivo. II. Regulation of tumor necrosis factor and interleukin-1 alpha/beta expression and suppression. 224 Jan 64

Glucocorticoids inhibit the migration of neutrophils induced by endotoxin (E. coli lipopolysaccharide, LPS) in vivo. Macrophage monolayers stimulated by LPS showed a dose-dependent release into the supernatant of a chemotactic factor for neutrophils, MNCF, which was active in vivo and in vitro. Dexamethasone reduced the neutrophil migration into the abdominal cavities of rats that was induced by LPS, but did not affect the migration induced by MNCF. The release of MNCF by LPS-pretreated macrophage monolayers was inhibited by dexamethasone and hydrocortisone but not by indomethacin and BW755C. MNCF was stable at 56 degrees C and did not release histamine from mast cells. Thus, MNCF activity seems not to be due to arachidonic acid metabolites or C5/C5a. MNCF shares some properties with interleukin-I, such as the blockade of its release by glucocorticoids, the association of its activity with a material of a molecular weight greater than 10 000 Daltons and the abolition of its activity by incubation with phenylglyoxal. However MNCF liberation was not blocked by cycloheximide and the time course of its release by macrophage monolayers stimulated by LPS differed from that described for interleukin-1. In addition human interleukin-1 when tested in dexamethasone-treated test rats failed to induce neutrophil migration. It is suggested that inhibition by glucocorticoids of LPS-induced neutrophil migration in vivo is not due to a direct effect upon the migrating cells but rather to an indirect one, i.e. through blockade of MNCF release by macrophages.
 ...
PMID:The release of a neutrophil chemotactic factor from peritoneal macrophages by endotoxin: inhibition by glucocorticoids. 242 49

When stimulated with lipopolysaccharide (LPS), primary cultures of Kupffer cells from the rat secreted a hepatocyte-stimulating factor (Kupffer factor) which induced the synthesis of alpha 2-macroglobulin (a2M) by hepatocytes. The effect of this Kupffer factor was found only when dexamethasone was present in the hepatocyte culture medium. Dexamethasone alone stimulated the a2M synthesis, to some extent, in a dose-dependent manner. When both Dex and the Kupffer factor were added to the medium, cultured hepatocytes synthesized 100-fold a2M, quantitative evidence that explains the in vivo phenomenon in which the serum a2M concentration increases more than 100-fold in the acute phase. A co-culture study with hepatocytes and Kupffer cells indicated that the latter cells have a major function in the induction of a2M synthesis in vivo. A hybridization study with rat a2M cDNA showed that the concentration of mRNA increased in cultured hepatocytes in the presence of the Kupffer factor, but only when dexamethasone was present. From these results we concluded that Kupffer cells secrete a hepatocyte-stimulating factor when stimulated by LPS and that glucocorticoid is essential for the induction of a2M in rat hepatocytes. The effect of the Kupffer factor and glucocorticoid appears to be regulated in the pretranslational, probably the transcriptional, phase.
 ...
PMID:Kupffer cell stimulation of alpha 2-macroglobulin synthesis in rat hepatocytes and the role of glucocorticoid. 243 19

Human hepatoma (HepG2) cells respond to unfractionated conditioned media of human squamous carcinoma (COLO-16) cells and lipopolysaccharide-stimulated human peripheral blood monocytes by increasing the synthesis of alpha 1-acid glycoprotein, haptoglobin, complement C3, alpha 1-antichymotrypsin, alpha 1-antitrypsin, and fibrinogen, while decreasing the synthesis of albumin. The regulation of the acute phase proteins is mediated by hepatocyte-stimulating factors (HSF) and interleukin 1 (IL-1) present in the conditioned medium. Purified HSF-I from COLO-16 cells stimulates preferentially alpha 1-acid glycoprotein synthesis, whereas COLO-HSF-II stimulates preferentially the synthesis of haptoglobin, fibrinogen, and alpha 1-antitrypsin. HSF from monocytes, which has been identified as interferon-beta 2 (B cell stimulating factor-2), displayed the same activity as COLO-HSF-II. Dexamethasone alone had no effect on acute phase plasma protein synthesis but enhanced the response to various HSF severalfold. IL-1 had a relatively low stimulatory activity on the synthesis of alpha 1-acid glycoprotein, haptoglobin, and alpha 1-antichymotrypsin but strongly reduced the basal expression of fibrinogen. The only synergistic action between IL-1 and HSF (or interferon-beta 2) was noted for the synthesis of alpha 1-acid glycoprotein. Tumor necrosis factor active on other hepatic cells failed to modulate significantly the expression of any plasma proteins in HepG2 cells. These studies showed that for an optimal HepG2-cell response a combination of HSF (or interferon-beta 2), IL-1, and dexamethasone is needed. This finding might indicate the identity of some of those hormones involved in regulation of the hepatic acute phase response in vivo.
 ...
PMID:Interaction among hepatocyte-stimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (HepG2) cells. 244 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>