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)

Tumor necrosis factor-alpha (TNF-alpha) has been shown to contribute to the alcohol [ethanol (ETOH)]-induced alteration of hepatic function. Therefore we tested the hypothesis that the hepatic action of TNF-alpha could be due, at least in part, to alterations in TNF-alpha cell-surface receptors of hepatic parenchymal (hepatocytes) and nonparenchymal (Kupffer and sinusoidal endothelial) cells. Rats were either acutely treated with ETOH by a primed, continuous 7-hr intravenous infusion of 20% (w/v) ETOH (30 mg/100 g body weight/h) or chronically fed an ETOH-containing liquid diet (5.2% ETOH, w/v, with ETOH as 36% of total calories) for 14 weeks. Control rats in the acute group were infused with sterile saline, whereas control rats in the chronic group were fed liquid diet containing dextrin to replace ETOH in isocaloric amounts. Three hr before killing, the rats were injected intravenously with Gram-negative bacterial lipopolysaccharide [(LPS) 100 micrograms/100 g body weight] or saline. Hepatocytes, Kupffer cells, and sinusoidal endothelial cells were isolated after liver perfusion with collagenase (without pronase), separated by centrifugal elutriation, and used to determine the affinity (Kd) and capacity (Bmax) of binding sites, using recombinant human-[125I]TNF-alpha as the ligand. Two binding sites were detected on Kupffer cells and sinusoidal endothelial cells isolated from control animals: a high-affinity (Kd1, in the range of 150-200 pM), low-capacity (Bmax, in the range of 2-3 fmol/10(6) cells) binding site and a low-affinity (Kd2, in the range of 2-9 nM), high-capacity (Bmax2, in the range of 3-15 fmol/10(6) cells) binding site.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tumor necrosis factor-alpha cell-surface receptors of liver parenchymal and nonparenchymal cells during acute and chronic alcohol administration to rats. 762 65

Tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) modulate immune responses, as TNF is postulated as a first messenger for priming immune cells and IFN as the second messenger for activation. Nitric oxide (NO) is also an important mediator of immune function, as NO produced by immune cells in response to cytokines such as TNF and IFN may be a cytotoxic end-product effector of immune activation. To examine TNF and IFN modulation of NO production and effects upon allograft survival, we studied the in vitro effect of TNF, IFN, and lipopolysaccharide (LPS, as a nonspecific immune stimulator and TNF promoter) singly or together on NO production in unstimulated rat splenocytes or in response to allogeneic stimulation in MHC mismatch (Brown-Norway, BN, vs Lewis, LEW) mixed lymphocyte reactions. Nitrite as a stable reaction product of NO was determined by a colorimetric method based on the Griess reaction. Interestingly, unstimulated cells had little NO production in response to TNF or IFN; however, following nonspecific (LPS) or allogeneic stimulation there was a significant upregulation of NO production that was synergistically enhanced by the presence of both TNF and IFN. Significantly, anti-TNF antibody inhibited NO production up to 60% in all groups. In vivo studies used a cardiac heterotopic allotransplant model, again BN to LEW. Control recipients received no immunotherapy. Experimental recipients received IFN alone, anti-IFN antibody, anti-TNF antibody, or anti-TNF and anti-IFN antibody. Results from these allograft experiments showed no influence on survival by IFN alone or anti-IFN antibody alone.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tumor necrosis factor-alpha and interferon-gamma modulation of nitric oxide and allograft survival. 763 Jan 11

Tumor necrosis factor-alpha (TNF-alpha) exerts a wide spectrum of biological activities and contributes to the pathophysiology of septic shock. We studied whether milrinone suppresses TNF-alpha and IL-1 beta releases from mouse peritoneal macrophages. Mouse peritoneal macrophages were stimulated for 18 hr with lipopolysaccharide and different doses of milrinone. TNF-alpha release was suppressed in a dose-dependent fashion with milrinone, reaching half-maximal inhibition at 30 microM. Release of IL-1 beta was not suppressed with 25 microM of milrinone, but it was suppressed with 250 microM of milrinone. We conclude that TNF-alpha release is suppressed by therapeutically administered milrinone.
 ...
PMID:[Milrinone suppresses TNF-alpha and IL-1 beta release in mouse peritoneal macrophages]. 763 54

Tumor necrosis factor-alpha (TNF), originally identified as an inflammation-associated cytokine, is synthesized throughout the female reproductive tract as well as in placentas and embryos. Development, female sex steroid hormones, and lipopolysaccharide influence expression of this gene. The functions of TNF may be determined in part by differential expression of the two species of TNF receptors, both of which seem to be regulated by female sex steroid hormones. Evidence has accumulated that supports a role for this potent, pleiotropic cytokine in autocrine and paracrine processes central to reproduction, including gamete and follicle development, steroidogenesis, uterine cyclicity, placental differentiation, development of the embryo, and parturition.
 ...
PMID:Tumor necrosis factor-alpha in the female reproductive tract. 763 40

Pichinde virus (PIC) is a reticuloendothelial arenavirus of the New World tropics. A guinea pig passage-adapted strain of this virus (adPIC) is uniformly lethal for inbred guinea pigs, while the related, prototype strain (PIC3739) has attenuated virulence. The abilities of adPIC and PIC3739 to induce tumor necrosis factor (TNF) in vivo and in cultured macrophages were compared. Infection with adPIC, but not PIC3739, was associated with detectable serum TNF that peaked in week 2 of infection. Tumor necrosis factor was found in the spleens of adPIC- and PIC3739-infected animals in week 1 of infection; TNF alpha mRNA levels in spleens and livers of adPIC infected animals increased and remained high throughout infection, whereas PIC3739-infected organs showed down regulation of TNF alpha mRNA late in infection. Peritoneal macrophages explanted from adPIC-infected animals showed enhanced lipopolysaccharide-inducible TNF production. Altered regulation of TNF production may play a role in the pathogenesis of guinea pig arenavirus disease.
 ...
PMID:Tumor necrosis factor and the pathogenesis of Pichinde virus infection in guinea pigs. 769 69

Tumor necrosis factor-alpha (TNF) exerts a wide spectrum of biological activities and contributes to the pathophysiology of septic shock. Elevated circulating levels of TNF have also been reported in patients with severe chronic heart failure. We studied the effect of amrinone, a class III cyclic nucleotide phosphodiesterase inhibitor used in the treatment of acute heart failure, on the synthesis of TNF in vitro. Peripheral blood mononuclear cells from healthy volunteers or cells of a permanent monoblast cell line were stimulated for 20 h with bacterial lipopolysaccharide and different doses of amrinone. TNF production is suppressed in a dose-dependent manner to a minimum of 9% of controls with 1000 microM of amrinone, reaching half-maximal inhibition at 80 microM amrinone. This effect appears to be mediated via cAMP, which accumulated nearly twofold in the presence of amrinone. Suppression of TNF synthesis by therapeutically administered phosphodiesterase inhibitors such as amrinone may contribute to their beneficial effect in the treatment of heart failure.
 ...
PMID:Amrinone suppresses the synthesis of tumor necrosis factor-alpha in human mononuclear cells. 774 41

Tumor necrosis factor-alpha (TNF) may activate human immunodeficiency virus (HIV), antagonize zidovudine activity, and contribute to AIDS wasting syndrome. Pentoxifylline decreases TNF production. In cell culture, pentoxifylline decreases HIV replication and gene expression. Since an AIDS Clinical Trial Group study suggested that pentoxifylline (400 mg thrice daily) is safe in AIDS patients and decreases TNF mRNA levels in peripheral blood mononuclear cells (PBMC), a second cohort received 800 mg thrice daily for 8 weeks. During treatment, the median decrease in TNF production by PBMC cultured with 0.1 microgram/mL lipopolysaccharide (LPS) was 40%. The median change in TNF mRNA was a 34% decrease. Pentoxifylline did not affect HIV levels as detected by quantitative microculture or serum p24 antigen measurements, nor did it alter zidovudine pharmacokinetics. The most common toxicity was gastrointestinal. Pentoxifylline at dosages of less than thrice-daily 800 mg is well tolerated and may decrease TNF mRNA levels and LPS-induced TNF production.
 ...
PMID:High-dose pentoxifylline in patients with AIDS: inhibition of tumor necrosis factor production. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. 776 5

Tumor necrosis factor-alpha (TNF-alpha) is a powerful macrophage-derived proinflammatory cytokine, via both direct effects on host tissues as well as indirectly through the induction of other proinflammatory mediators, including interleukin- (IL) 1 beta and IL-6. Activation of murine bone marrow-derived macrophages (BMDM phi) with lipopolysaccharide (LPS) causes rapid expression of TNF-alpha, which as an autocrine factor enhances BMDM phi function through IL-1 beta and IL-6 production. In this study, we have examined the specific transcriptional inhibition of BMDM phi TNF-alpha using novel enantiomeric carbocyclic nucleoside analogues. BMDM phi were derived in vitro from murine bone marrow progenitors using colony stimulating factor-1 and treated with combinations of LPS (1-100 nG/ml) and the enantiomeric carbocyclic nucleoside (10-100 microM) analogues MDL 201, 112 (9-[(1S,3R)-cis-cyclopentan-3-ol]adenine); MDL 201,451 (9-[1R,3S)-cis-cyclopentan-3-ol]adenine); MDL 201,449 (9-[(1R,3R)-trans-cyclopentan-3-ol]adenine) and MDL 201,484 (9-[(1S,3S)-trans-cyclopentan-3-ol]adenine). Northern blot analysis showed that MDL 201,449 was the most effective agent in vitro at selectively inhibiting TNF-alpha. MDL 201,449 reduced TNF-alpha mRNA levels by nearly 50% for up to 4 hr after the simultaneous addition of LPS and the synthetic agent. In contrast, mRNA and secreted protein levels for IL-1 beta (measured by the D10.S bioassay) and mRNA for TNF-alpha receptor p60 and TNF-alpha receptor p80 were not significantly affected. Carbocyclic nucleoside analogues were effective when added to BMDM phi up-to 2 hr after LPS treatment and at concentrations as low as 10 microM. Regulation of BMDM phi IL-6 by carbocyclic nucleoside analogues in response to LPS appears to be both concentration and time dependent, because IL-6 mRNA and secreted protein levels were inhibited at only high drug concentrations (100 microM) and effective only at longer exposure times (+4 hr of incubation) to LPS. These data support the concept that M phi-derived proinflammatory cytokine gene expression is differentially, rather than coordinately, regulated by selective signal transduction and/or molecular pathways. Enantiomeric carbocyclic nucleoside analogues that specifically inhibit TNF-alpha may have therapeutic potential in inflammatory diseases, such as systemic inflammatory response syndrome, where TNF-alpha has been shown to have an important role in initiating the early stages of disease.
 ...
PMID:Specific transcriptional inhibition of bone marrow-derived macrophage tumor necrosis factor-alpha gene expression and protein production using novel enantiomeric carbocyclic nucleoside analogues. 779 Nov 26

Endothelial damage, synovial oedema, fibrin deposition, polymorphonuclear cell (PMN) invasion, and mild lining cell hyperplasia characterize acute inflammatory arthritis. Later on, perivascular tissue is infiltrated by mononuclear cells. The early events are mediated by interactions between PMNs and endothelial cells. Both parts in the adhesion event are activated with multiple stimuli resulting in complex interactions of varying intensity and duration. Adhesion molecules present on the surface of PMNs (L-selectin) or induced by inflammatory stimuli (beta 2-integrins) mediate PMN adhesion to activated endothelium, which has counter receptors (E-selectin for L-selectin and ICAM-1 and ICAM-2 for beta 2-integrins). At the initial phase L-selectin initiates the rolling of PMNs on endothelial cells. Further stimuli result in a more prolonged adhesion between PMNs and endothelium. At the side of endothelium, induction of P-selectin and PAF by histamine, thrombin and LTC4 contribute to the acute rolling of PMNs on endothelial surface. Tumor necrosis factor (TNF), interleukin-1 (IL-1) and lipopolysaccharide activate endothelial cells to synthesize interleukin-8 (IL-8), a potent chemotactic and proadhesive mediator for PMNs, and further adhesion molecule (E-selectin), a mediator of long-term adhesion between PMN and endothelium. After adhesion and migration to the focus of inflammation, PMNs induce inflammation by aggregating, releasing hydrolyzing enzymes, generating lipid peroxidation products such as prostaglandins and LTB4, and oxygen derived free radicals. In studies on the pathogenesis of seronegative spondyloarthropathies, we have shown persistently aberrant PMN function evidenced by enhanced chemotaxis and high production of toxic oxygen derived free radicals by PMN.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The present knowledge of the inflammatory process and the inflammatory mediators. 781 74

Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic response to injury and infection, is a primary mediator of endotoxin-induced hemodynamic instability. Two types of naturally occurring soluble TNF receptors circulate in human experimental endotoxemia and the recombinant proteins of both have been hypothesized as potential therapeutic agents antagonizing TNF-mediated effects of endotoxemia. The administration of recombinant sTNFr-I has been previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In the current study, we investigated the role of recombinant sTNFR-II at low (0.5 mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated for continuous blood pressure monitoring and cardiac output measurement by thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at 0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS caused a 30% decrease in mean arterial pressure by 60 min, which began to recover by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals, were significantly increased by sTNFr-II compared to LPS alone. Serum from animals treated with high-dose sTNFr-II showed significantly less TNF cytotoxicity than those treated with low-dose sTNFr-II, indicating that high doses of sTNFr-II are required for the inhibition of the bioactivity of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated hemodynamic instability. 783 Apr 6


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