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)

Endothelial cell activation antigens may play important roles in immune responses and in inflammation. This report describes the identification and characterization of a monoclonal antibody, named EAA-B, which reacts specifically with human umbilical vein endothelial (HUVE) cells pre-treated with tumour necrosis factor-alpha (TNF-alpha) but not with untreated cells. The expression of the EAA-B antigen on HUVE cells could also be induced by interleukin-1 (IL-1), bacterial lipopolysaccharide (LPS), and phorbol esters but not by interferon-gamma (IFN-gamma). By contrast, EAA-B antigen expression on neonatal foreskin and rheumatoid synovial fibroblasts, whether pre-treated with TNF-alpha or not, was not detectable. Peripheral blood leucocytes and the leukaemic cell lines U937, HL-60, Raji and Molt 4 showed no detectable expression of the EAA-B antigen. Kinetic studies demonstrated that the EAA-B antigen was rapidly expressed, peaked at 6 hr and declined to basal level by 24 hr. Western blotting revealed that monoclonal antibody EAA-B recognized a polypeptide of approximately 80,000-90,000 MW. EAA-B partially blocked the augmented adhesion of HL-60 cells to TNF-treated HUVE cells. However, it failed to inhibit the enhanced binding of peripheral blood leucocytes, U937, Raji and Molt 4 Cells to TNF-treated HUVE cells. In situ, the EAA-B antigen was detected on some vascular endothelium in tonsils, lymph nodes, psoriatic skin and rheumatoid synovium but not in normal non-lymphoid tissues. Interestingly EAA-B antigen is also expressed by B lymphocytes in germinal follicle centres (GFC) of lymphoid tissues. The co-expression of this endothelial activation antigen by GFC B lymphocytes may have significant implications for immune responses and in B-lymphocyte differentiation.
 ...
PMID:Identification of a human endothelial cell activation antigen that is co-expressed by germinal follicle centre B lymphocytes. 139 50

1. A closed system was developed for perfusing J774 macrophages in columns. The cells were perfused for up to 100 h, at which time they were still viable. 2. Stimulation with increasing concentrations (0.01-10 micrograms ml-1) of bacterial lipopolysaccharide (LPS) caused the cells to produce increasing amounts of nitrite in the perfusion medium. This production was time-dependent, reaching a plateau by 48-50 h. 3. The nitrite accumulation caused by 0.1 microgram ml-1 of LPS was augmented by priming the cells for 2 h with increasing amounts of interferon-gamma. The nitrite accumulation also reached a plateau under these conditions. 4. N-iminoethyl-L-ornithine (L-NIO, 30 microM) completely inhibited the accumulation of nitrite whereas dexamethasone (0.3 microM) caused 60-70% inhibition. 5. Perfusion of the cells without L-arginine prevented the nitrite accumulation. Replacement of this amino acid after 20 or 50 h of perfusion led to a rapid generation of nitrite, the levels of which continued to increase for the duration of the experiment. 6. Thus, the perfusion system can be used to study the kinetics of the activation of the NO synthase and most likely other parameters in J774 cells and probably other cells in culture. An observation already of interest is that the 'disappearance' of the NO synthase after its activation can be prevented or reduced by removal of L-arginine from the medium.
 ...
PMID:A perfusion system for the long term study of macrophage activation. 142 83

Macrophages collected from BCG-infected mice or exposed in vitro to interferon-gamma plus lipopolysaccharide developed a cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. This trypanostatic activity of activated macrophages was inhibited by addition of N-monomethyl-L-arginine, an inhibitor of the L-arginine-nitric oxide (NO) metabolic pathway, indicating a role for NO as the effector molecule. Contrary to trypanosomes treated with N2gas, trypanosomes treated with NO gas did not proliferate in vitro on normal macrophages. Compared to mice infected with control parasites, mice infected with NO-treated parasites had decreased parasitemias in the first days postinfection and had a prolonged survival. Addition of excess iron reversed the trypanostatic effect of both activated macrophages and NO gas. These data show that activated macrophages exert an antimicrobial effect on T.b. gambiense and T.b. brucei through the L-arginine-NO metabolic pathway. In trypanosomes, NO could trigger iron loss from critical targets involved in parasite division. The participation of this effector mechanism among the other immune elements involved in the control of African trypanosomes (antibodies, complement, phagocytic events) remains to be defined.
 ...
PMID:Nitric oxide-mediated cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. 142 37

The effects of lipopolysaccharide (LPS), recombinant human tumor necrosis factor-alpha (TNF), recombinant human interleukin 1-beta (IL-1 beta), and interferon-gamma (IFN-gamma) on IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA) and by Northern blot analysis in cultured human dermal microvascular endothelial cells (HDMEC). Unstimulated HDMEC did not produce significant amounts of IL-6, whereas lipopolysaccharide (LPS), TNF, and IL-1 beta were potent inducers of HDMEC-derived IL-6 production. Treatment with IFN-gamma had no effect. IL-1 beta stimulation resulted in pronounced IL-6 production after 4 h, followed by complete downregulation at the transcriptional level after 24 h. In contrast, LPS and TNF induced prolonged stimulation of IL-6 production by HDMEC as IL-6 mRNA transcripts were still detected after 24 h treatment and IL-6 protein was markedly increased at this timepoint. The effects of hydrocortisone, dexamethasone, calcitriol, acitretin, and cyclosporin A on TNF- or IL-1 beta-induced IL-6 production by HDMEC were determined by ELISA. Both hydrocortisone and dexamethasone dose-dependently inhibited the cytokine-induced IL-6 production, whereas the inhibition by calcitriol was less pronounced. In contrast, acitretin and cyclosporine A had no influence on cytokine-induced HDMEC IL-6 production. These results disclose dermal endothelial cells as a major source for the pro-inflammatory cytokine IL-6, involved in the regulation of inflammatory skin processes. As IL-6 seems to play a key role in the pathogenesis of psoriasis, the beneficial effects of corticosteroids and calcitriol in this disease may partly be explained by their ability to inhibit HDMEC-derived IL-6 production.
 ...
PMID:Cytokine-stimulated human dermal microvascular endothelial cells produce interleukin 6--inhibition by hydrocortisone, dexamethasone, and calcitriol. 143 Dec 12

CD14 has been reported to be the lipopolysaccharide (LPS)-LPS binding protein receptor. The effects of interferon-gamma (IFN-gamma) on CD14 expression have not been clearly established. The purpose of this investigation was to examine the effects of IFN-gamma alone and IFN-gamma followed by bacterial LPS on CD14 expression. Human peripheral blood monocytes were isolated by counterflow centrifugal elutriation (CCE). Monocytes were cultured for 48 h with IFN-gamma alone or for 24 h with IFN-gamma followed by LPS for a second 24 h. IFN-gamma alone caused a down-regulation of CD14 expression, as assessed by flow cytometry, relative to CD14 expression in untreated monocytes. In addition, CD14 expression was even more significantly down-regulated after IFN-gamma pretreatment followed by either Prevotella intermedia or Salmonella typhimurium LPS. Likewise, the percentage of CD14+ monocytes decreased after IFN-gamma alone and even more dramatically after IFN-gamma treatment followed by either LPS. This study clearly demonstrated that IFN-gamma down-regulates CD14 expression and that LPS following IFN-gamma pretreatment potentiates this effect.
 ...
PMID:The effects of interferon-gamma and bacterial lipopolysaccharide on CD14 expression in human monocytes. 143 9

1 alpha, 25-Dihydroxyvitamin D3 (D3) (100 nM) and interferon-gamma (IFN-gamma) (100 U/ml) cooperatively inhibited the proliferation of HL-60 cells, and synergistically induced their monocytic differentiation. The growth-promoting effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) (10 ng/ml) was inhibited appreciably by D3 and slightly by IFN-gamma. Despite the clear difference in their effects on growth of HL-60 cells, both IFN-gamma and GM-CSF in combination with D3 induced cell cycle changes, decreasing the number of cells in the S phase and increasing their percentage in the G1/0 phase. GM-CSF alone had no effect on differentiation, but enhanced differentiation induced by D3 distinctly though to a limited extent, and also enhanced monocytic differentiation, including morphological changes of HL-60 cells in the presence of D3 and IFN-gamma. GM-CSF as well as D3 and IFN-gamma induced interleukin-1 beta (IL-1 beta) production by the HL-60 cells, clearly indicating their importance in differentiation of these cells. IFN-gamma and GM-CSF had mutually potentiating effects and induced maximum IL-1 beta production in response to lipopolysaccharide (LPS) in the presence of D3. Thus despite its growth-promoting effect, GM-CSF is a potential inducer of monocytic differentiation of human myeloid leukemia cells, because in cooperation with IFN-gamma it induced monocyte-macrophage differentiation of HL-60 cells in the presence of D3.
 ...
PMID:The role of granulocyte-macrophage colony-stimulating factor in induction of monocytic differentiation of HL-60 cells: synergistic interaction with 1 alpha, 25-dihydroxyvitamin D3 and interferon-gamma in inducing interleukin-1 beta. 144 89

Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing.
 ...
PMID:Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure. 145 75

Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of a number of lympho-haemapoietic cytokines, including CSF-1, interleukin-6 (IL-6) and leukaemia inhibitory factor (LIF) now known to be synthesized by epithelial cells in the murine uterus. GM-CSF synthesis is regulated primarily by the ovarian steroid hormone oestrogen, but is also subject to modulation by factors including a seminal component of seminal vesicle origin which stimulates a 20-fold increase in luminal fluid content at mating, and bacterial lipopolysaccharide (LPS) and the T-lymphocyte and natural killer (NK) cell product interferon-gamma (IFN gamma). In the non-pregnant mouse GM-CSF synthesis peaks at oestrus. Synthesis is maintained at comparable or moderately higher levels during the preimplantation period of pregnancy and in the non-decidualized endometrium during mid gestation. An embryotrophic activity is suggested by studies in vitro that indicate that GM-CSF stimulates attachment and outgrowth of blastocysts. It is postulated that GM-CSF is of major importance to the physiology of pregnancy through its role as a component of a local cytokine circuit acting to recruit and regulate function of endometrial leukocytes, and by its action as interlocutor and important effector arm in embryo-maternal interactions during gestation.
 ...
PMID:Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus. 146 94

After activation by interferon-gamma (INF-gamma) and lipopolysaccharide(LPS), mouse peritoneal macrophages were cocultured with P388 parental cell line (P388/PRT) and its adriamycin (ADM)-, cisplatin(CDDP)-, cyclophosphamide(CPM)-, and mitomycin-C(MMC)-resistant cell lines for one day at effector:target ratios (E:T) of 10:1, 5:1, and 2:1. The direct 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cleavage assay and a new indirect MTT assay as well as clonogenic assay were used to quantitate activated macrophage-mediated cytotoxicity to these non-adherent leukemia targets. The results revealed that all the P388 cell lines can be suppressed efficiently by activated macrophages, but P388 CPM- and MMC-resistant cell lines (P388/CPM, P388/MMC) were more susceptible than P388/PRT while P388 ADM- and CDDP-resistant cell lines (P388/ADM, P388/CDDP) shared equal level of survival rates with P388/PRT. This study also showed that both non-activated and activated macrophages can produce formazan in a high level, which can interfere with the final results of direct MTT assay. The new indirect MTT assay can avoid such interference by separating the effectors from the targets before performing the MTT assay and reflects the real viability of the targets so the indirect MTT assay developed in this study could be a better way to examine cytostatic and cytotoxic effect of activated macrophages on non-adherent tumor cells in vitro.
 ...
PMID:Differential macrophage-mediated cytotoxicity to P388 leukemia cells and its drug-resistant cells examined by a new MTT assay. 146 25

Accumulation of quinolinic acid and neuroactive kynurenines derived from tryptophan are of potential significance in human neuropathologic diseases because of their neurotoxic and convulsant properties. Clinical studies have established that sustained elevations of quinolinic acid, L-kynurenine and kynurenic acid within the cerebrospinal fluid occur in patients with a broad spectrum of inflammatory diseases and correlate with markers of immune activation and interferon-gamma activity. The present study describes an animal model that replicates these clinical observations and investigates the role of interferon-gamma as a mediator between immune activation and increased kynurenine pathway metabolism. Marked elevations in quinolinic acid, L-kynurenine and 3-hydroxykynurenine as well as an increased ratio of quinolinic acid: kynurenic acid in brain occurred 24 h after systemic pokeweed mitogen administration to C57BL6 mice. In plasma, L-tryptophan and kynurenic acid levels were reduced by pokeweed mitogen, while the concentrations of L-kynurenine, 3-hydroxykynurenine and quinolinic acid were increased. Interferon-gamma, pokeweed mitogen and lipopolysaccharide induced indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway, and increased both L-kynurenine and quinolinic acid concentrations of brain and systemic tissues, particularly in the lung, gastrointestinal tract and spleen. In contrast, hepatic tryptophan-2,3-dioxygenase activity was either reduced or unaffected. Increases in kynurenine pathway metabolism were sustained in mice given daily injections of interferon-gamma for seven days and subsequent responses to interferon-gamma were further enhanced. In contrast, daily administration of lipopolysaccharide was associated with subsequent attenuated responsiveness (tolerance) to lipopolysaccharide, pokeweed mitogen and interferon-gamma. Systemic administration of a monoclonal antibody to mouse interferon-gamma either attenuated or abolished the responses of kynurenine pathway metabolism to pokeweed mitogen and interferon-gamma. We conclude that acute and chronic increases in quinolinic acid and neuroactive kynurenines follow immune stimulation in mice, and result from indoleamine-2,3-dioxygenase induction. The results demonstrate that interferon-gamma is an important mediator between immune stimulation and indoleamine-2,3-dioxygenase induction. These increases in kynurenine pathway metabolism closely parallel the responses documented in patients with a broad spectrum of inflammatory diseases. Mice treated with immune stimuli are a useful model to investigate the relationships between immune activation and kynurenine pathway metabolism.
 ...
PMID:Effects of immune activation on quinolinic acid and neuroactive kynurenines in the mouse. 146 84


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