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)

The influence of mononuclear cell supernatants (MNCS) from nine healthy donors and 35 HIV-infected patients (17 with lymphoadenopathy syndrome (LAS), 15 with ARC and three with AIDS) on functional activity of polymorphonuclear neutrophils (PMN) from healthy donors was investigated. MNC after short-term cultivation (24 h) produced factors which enhanced chemiluminescence (CL) and chemotaxis of PMN. This augmentation did not depend on stimulation of MNC by mitogens (lipopolysaccharide Escherichia coli (LPS) and concanavalin A (Con A)) or on activation of PMN by FMLP. After 48 h of cultivation only MNC stimulated by LPS produced these factors. MNCS from HIV-infected patients provoked a more pronounced augmentation of PMN CL compared with MNCS from healthy subjects. This enhancement was observed in patients at all stages of infection, but was more pronounced in patients with LAS. MNCS impact on PMN CL was not connected with proliferative activity of MNC but was correlated with the level of CD4 cells. It was shown that removal of adherent cells from MNC fraction resulted in decreased MNCS impact. Treatment of MNCS by antibody to IL-1 beta, IL-8, interferon-alpha (IFN-alpha) and tumour necrosis factor-alpha (TNF-alpha) did not decrease MNCS impact on PMN CL.
 ...
PMID:Mononuclear cells from HIV-infected patients produce factors which enhance functional activity of polymorphonuclear neutrophils from healthy subjects. 132 4

The central importance of xanthine dehydrogenase (XDH) and xanthine oxidase (XO) in the pathobiochemistry of a number of clinical disorders underscores the need for a comprehensive understanding of the regulation of their expression. This study was undertaken to examine the effects of cytokines on XDH/XO activity and gene expression in pulmonary endothelial cells. The results indicate that IFN-gamma is a potent inducer of XDH/XO activity in rat lung endothelial cells derived from both the microvasculature (LMVC) and the pulmonary artery. In contrast, interferon-alpha/beta, tumor necrosis factor-alpha, interleukin-1 or -6, lipopolysaccharide and phorbol myristate acetate have no demonstrable effect. The increase in XDH/XO activity requires new protein synthesis. By Northern analysis, IFN-gamma markedly increases the level of the 5.0-kb XDH/XO mRNA in LMVC. The increase is due, in part, to increased transcription rate of the XDH/XO gene. Transcriptional activation does not require new protein synthesis. The physiologic relevance of these observations was evaluated by administering IFN-gamma to rats. Intraperitoneal administration leads to an increased XDH/XO activity and XDH/XO mRNA level in rat lungs. In sum, IFN-gamma is a potent and biologically relevant inducer of XDH/XO expression; the major site of upregulation occurs at the transcriptional level.
 ...
PMID:Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells. 137 Feb 94

Exogenous interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta) (type I IFNs) are known to suppress the IFN-gamma-dependent expression of class II MHC (Ia) antigens on macrophages (M phi). We report here that the endogenous type I IFNs produced by M phi in response to IFN inducers regulate Ia expression of the M phi themselves. Coculture of M phi with IFN-gamma and polyinosinic-polycytidylic acid [poly(I):poly(C)] resulted in the reduction of Ia expression in comparison with those cultured without poly(I):poly(C). Pretreatment of M phi with poly(I):poly(C) or a bacterial lipopolysaccharide (LPS), which is also a potent IFN inducer, in vitro or in vivo, before being exposed to IFN-gamma was also effective in suppressing the Ia expression. Such suppression was abolished by the addition of anti-IFN-alpha/beta antibodies to the M phi culture along with IFN-gamma. M phi cultured with L-cell conditioned medium (LCM) containing M-CSF were less capable of expressing Ia antigens than those cultured without LCM. The Ia-expressing ability of LCM-treated M phi was also restored by the addition of anti-IFN-alpha/beta antibodies. M phi in the early stage of sterile inflammation were less responsive to IFN-gamma than those in the late stage. These results suggest that endogenous type I IFNs, which are produced in response to natural or synthetic IFN-inducers, regulate M phi Ia expression in an autocrinal manner.
 ...
PMID:Suppression of macrophage Ia antigen expression by endogenous interferon-alpha/beta. 137 84

Endotoxins, the lipopolysaccharide (LPS) moieties on the bacterial cell wall, cause many of the pathological features of Gram-negative septicemia. Tumor necrosis factor (TNF), primarily a product of monocyte/macrophages, has been shown to mediate many of the pathophysiological effects of endotoxin. Kupffer cells, the largest macrophage population in the body, release TNF when stimulated by LPS in vitro. A recombinant human hybrid interferon-alpha A/D (rIFN-alpha) markedly inhibited this LPS-elicited TNF production by Kupffer cells. The effects of rIFN-alpha were further tested in C57BL/6 mice receiving a lethal dose (400 micrograms/mouse) of LPS. All LPS-treated mice died within 2 days. Pretreatment with rIFN-alpha 1 h before LPS challenge improved the survival at 3 days to 22% (5/23, p < 0.04). In contrast, rIFN-alpha was more effective when administered 20 min after LPS injection, increasing the survival rate to 81% (13/16, p < 0.0001). TNF mRNA expression in the liver and spleen 50 min after LPS challenge, and plasma TNF 1.5 h after LPS were also reduced by either pretreatment or post-treatment with rIFN-alpha. Subsequently, experiments were carried out to test the efficacy of delayed rIFN-alpha treatment. A significant protective effect was still apparent when rIFN-alpha was administered 6, 10 and even 14 h (81%, 62% and 28% survival, respectively) after LPS challenge when serum TNF levels had already returned to near baseline. These experimental results suggest that rIFN-alpha might have a therapeutic potential for the prevention and treatment of the deleterious effects associated with endotoxemia besides mechanisms initially blocking TNF production.
 ...
PMID:Interferon-alpha prevents endotoxin-induced mortality in mice. 144 3

Both interleukin-1 (IL-1) and endotoxin (lipopolysaccharide, LPS) are potent activators of the hypothalamo-pituitary-adrenal (HPA) axis, and they also increase cerebral norepinephrine metabolism and tryptophan. Injections of cause macrophages to synthesize and release various cytokines, including IL-1 and tumor necrosis factor alpha (TNF alpha). The hypothesis that macrophage production of IL-1 mediates the HPA-activating effect of LPS was tested in mice using the IL-1-receptor antagonist protein (IRAP). Administration of IRAP largely prevented the effects of IL-1 alpha or IL-1 beta on the elevation of plasma corticosterone and the concomitant increase in hypothalamic norepinephrine metabolism, but failed to alter the responses to LPS. IRAP did not prevent the increases in brain tryptophan that occurred after treatment with IL-1 or LPS. Recombinant human TNF alpha, TNF beta, IL-6, and interferon-alpha injected intraperitoneally failed to activate the HPA axis, but mouse TNF alpha was effective by this route, and human TNF alpha, TNF beta, and IL-6 were effective intravenously. None of these cytokines was as potent as IL-1. Pretreatment with an antibody specific for mouse TNF alpha, either alone or in combination with IRAP, also failed to prevent the elevation of plasma corticosterone by LPS. Thus, either IL-1 and TNF alpha are not involved in the HPA and noradrenergic responses to LPS, or there are alternative (redundant) pathways by which LPS can activate the HPA axis.
 ...
PMID:The role of interleukin-1 and tumor necrosis factor alpha in the neurochemical and neuroendocrine responses to endotoxin. 147 14

Highly purified natural human interferon-alpha (IFN-alpha) inhibited in a dose-dependent manner the proliferation of human peripheral blood lymphocytes (PBL) stimulated with T-cell mitogen concanavalin A (Con A) or with interleukin-2 (IL-2). Contrary to this inhibitory effect, IFN-alpha at the same concentrations significantly increased proliferation of PBL stimulated with B-cell mitogen bacterial lipopolysaccharide (LPS) or with IL-3, and even spontaneous proliferation of PBL was enhanced by IFN-alpha. Proliferation of Con A-stimulated PBL depleted of CD8+ cells was sensitive to the inhibitory action of IFN-alpha, while proliferation of the Con A-stimulated CD4+ cell-depleted PBL was not affected by IFN-alpha. The inhibitory effect of IFN-alpha on PBL proliferation was due to neither inhibition of IL-2 receptor (IL-2R) expression, activation of suppressor cells, nor inhibition of lymphokine production. Rather, IFN-alpha augmented production of IL-1 and IL-2 by PBL. These results show that the suppressive effect of natural IFN-alpha on Con A-induced proliferation of PBL is due to a direct growth-inhibitory effect on CD4+ T cells, and that IFN-alpha simultaneously augments production of lymphokines. This could in turn lead to the increased proliferation of IFN-alpha-resistant cell populations.
 ...
PMID:Inhibitory versus stimulatory effects of natural human interferon-alpha on proliferation of lymphocyte subpopulations. 153 94

The cDNA coding for xanthine dehydrogenase (XD) is isolated from mouse liver mRNA by cross-hybridization with a DNA fragment of the Drosophila melanogaster homologue. Two lambda bacteriophage overlapping clones represent the copy of a 4538-nucleotide-residue-long transcript with an open reading frame of 4005 nucleotide residues, coding for a putative polypeptide of 1335 amino acid residues. Comparison of the deduced amino acid sequence of the mouse XD with those of the Drosophila and the rat homologues shows a high conservation of this protein (55% identity between mouse and Drosophila, and 94% identity between mouse and rat). RNA blotting analysis demonstrates that interferon-alpha (IFN-alpha) and its inducers, i.e. poly(I).poly(C), bacterial lipopolysaccharide (LPS) and tilorone (2,7-bis-[2-(diethylamino)ethoxy]fluoren-9-one), increase the expression of XD mRNA in liver. Poly(I).poly(C) also induces XD mRNA in several other tissues in vivo. Protein synthesis de novo is not required for the elevation of XD mRNA after IFN-alpha treatment, since cycloheximide does not block the induction. The elevation of XD mRNA concentration is relatively fast and precedes the induction of both XD and xanthine oxidase (XO) enzymic activities.
 ...
PMID:Molecular cloning of a cDNA coding for mouse liver xanthine dehydrogenase. Regulation of its transcript by interferons in vivo. 159 Jul 74

It was recently reported that the opiate antagonist, naloxone (Nal), blocks the changes induced by the endogenous pyrogen, interferon-alpha 2 (IFN), in the electrical activity of hypothalamic thermosensitive neurons in rat brain slice preparations. This study was undertaken to determine whether the pyrogenic response to this cytokine might, therefore, be modulated through Nal-reversible opiate receptors. To examine this possibility, conscious guinea pigs were injected IV with recombinant human (rh) IFN (10 MU/animal), or, for comparison, with S. enteritidis endotoxin (lipopolysaccharide, LPS; 2 micrograms/kg), rh tumor necrosis factor-alpha (TNF; 20 micrograms/kg), or rh interleukin-6 (IL6; 50 micrograms/kg); Nal (10 mg/kg, SC) was administered immediately before the pyrogens. And also for comparison, in separate experiments, indomethacin (Indo; 10 mg/kg, IM) was injected 20 min before the pyrogens. Both Nal and Indo abolished the febrile rises evoked by IFN, TNF, and IL6. Nal reduced the first and suppressed the second of the characteristically bimodal febrile response to LPS; Indo depressed both peaks. Neither blocker had any significant thermal effect by itself. These results suggest that two processes may mediate the pyrogenic effects of these substances, viz., an endogenous opioid- and a PGE-dependent mechanism.
 ...
PMID:Neuromodulation of fever: apparent involvement of opioids. 201 82

High serum levels of endotoxin and cytokines, through which its activity is mediated, have been shown to be associated with disease severity in septic shock and in fulminant hepatic failure. In the present study, we have investigated the ability of activated charcoals (DHP-1 and Adsorba 150C) and uncharged resin (Amberlite XAD-7) to adsorb lipopolysaccharide (LPS) and various cytokines, namely tumour necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma). The capacities of the adsorbents were assessed by measurement of their equilibrium adsorption isotherms for these substances labelled with 125I. There was no single adsorbent that uniformly adsorbed LPS and the cytokines from phosphate buffered saline or human plasma. DHP-1 charcoal was superior to Adsorba 150C for all substances and was the most effective adsorbent for binding LPS, IL-1 alpha and IFN-gamma. Amberlite XAD-7 resin was most effective for TNF, IL-6 and IFN-alpha, but bound little LPS, particularly from human plasma. Ultrafiltration through a membrane which retains substances of molecular weight greater than 50 kD did not filter the cytokines from human plasma, although the molecular weight of the cytokines range from 17 to 22 kD. This demonstrated that, TNF, IL-1, IL-6, IFN-alpha and IFN-gamma readily bind to proteins and/or other large molecules in plasma.
 ...
PMID:Removal of endotoxin and cytokines by adsorbents and the effect of plasma protein binding. 203 48

Stimulation of bovine alveolar macrophages with calcium ionophore A23187 resulted in marked production of leukotriene (LT)B4 and a lesser increase in thromboxane (TX)B2, whereas opsonized zymosan (OPZ) resulted in production of TXB2 and relatively small increases in LTB4 and prostaglandin (PG)F2 alpha. Alveolar macrophages incubated with recombinant bovine interferon-gamma or lipopolysaccharide, and subsequently stimulated with A23187 or OPZ, had altered arachidonic acid metabolism, producing markedly increased amounts of TXB2 and PGF2 alpha, and slightly increased LTB4. Incubation of alveolar macrophages with lipopolysaccharide had a more profound effect on the increased amounts of TXB2 and PGF2 alpha, observed in response to stimulation with A23187 or OPZ, than did incubation with interferon-gamma. Alveolar macrophages incubated with recombinant bovine interferon-alpha 1-1 also produced slightly increased amounts of LTB4 when stimulated with A23187 or OPZ. Altered arachidonic acid metabolism by alveolar macrophages exposed to interferons and lipopolysaccharide may contribute to the development of pulmonary inflammation, such as in the early stages of bacterial pneumonia following viral infections that induce interferon production.
 ...
PMID:Modulation of arachidonic acid metabolism by bovine alveolar macrophages exposed to interferons and lipopolysaccharide. 217 51


1 2 3 4 5 6 7 Next >>