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 immunomodulator muramyl tripeptide-phosphatidylethanolamine (MTP-PE) has been shown to enhance host resistance against a variety of experimental infections and to cure influenza virus infection in mice when given in a single dose, even at a late stage of the disease. Tests of its capacity to induce alpha/beta- and gamma-interferon (IFN-alpha/beta and -gamma) in vitro demonstrated that it is neither an inducer nor a primer of IFN synthesis. On the contrary, we found that it inhibits the induction of IFN-alpha/beta and -gamma by poly(rI:rC), Newcastle disease virus, lipopolysaccharide, or concanavalin A in adherent cells from the peritoneal cavity and spleen of mice. The antiviral activity of already induced or exogenously added murine IFN was, however, not impaired.
 ...
PMID:Antagonism of interferon induction in spleen and adherent peritoneal cells of mice by the lipophilic antiviral muramyl peptide MTP-PE. 242 20

The influence of dynorphin A (DYN) and related opioid peptides on the tumoricidal function of activated murine peritoneal exudate macrophages (PEM) was investigated. Addition of DYN to macrophage cultures previously activated with mixed alpha + beta-interferon (IFN-alpha/beta) and bacterial lipopolysaccharide (LPS) significantly enhanced their ability to lyse P815 murine mastocytoma cells in a 16 hr chromium-release assay. The effects of DYN were dependent on prior macrophage activation. Peptide subfragments of DYN were effective in a manner similar to that of the 17-amino-acid parent molecule, indicating that peptide interaction with either kappa or delta-opioid receptors on the effector cell is effective in potentiating lytic function. The involvement of opiate receptors was confirmed by inhibition of the effects of DYN and leucine enkephalin by the opioid receptor antagonist naloxone. Finally, in addition to IFN-alpha/beta-primed macrophages, DYN also augmented tumoricidal function in PEM primed for cytotoxicity by either gamma-interferon (IFN-gamma) or the calcium ionophore A23187, indicating that DYN potentiates function in activated macrophages independent of the specific mode of activation.
 ...
PMID:Dynorphin and related opioid peptides enhance tumoricidal activity mediated by murine peritoneal macrophages. 243 27

Recombinant tumor necrosis factor alpha (rTNF alpha) and beta (rTNF beta) did not trigger H2O2 release from PMN in suspension. However, when PMN were plated on polystyrene surfaces coated with serum, fibronectin, vitronectin, laminin, or human umbilical vein endothelial cells (HUVEC), rTNFs induced a massive, prolonged secretory response, similar to that elicited by phorbol myristate acetate (PMA) or bacteria. On serum-coated plates, the maximum sustained rate of H2O2 release in response to rTNF alpha was 2.6 +/- 0.2 nmol/min per 10(6) PMN, the same as that with PMA; release continued for 73 +/- 4 min. On laminin-coated surfaces or HUVEC, release of H2O2 in response to rTNFs was slower, but lasted approximately 3.5 h, reaching the same total (greater than 100 nmol/10(6) PMN). Not only was this response far longer and larger than for other soluble stimuli of the respiratory burst studied with PMN in suspension, but the concentration necessary to elicit a half-maximal response (EC50) for rTNF alpha was orders of magnitude lower (55 pM). Responses were similar with FMLP, but ranged from zero to small with recombinant IFN alpha, recombinant IFN beta, recombinant IFN gamma, platelet-derived growth factor, recombinant IL-1 beta, or bacterial lipopolysaccharide. Adherent monocytes did not secrete H2O2 in response to rTNFs. H2O2 secretion by adherent PMN was first detectable 15-90 min after addition of rTNFs or FMLP. This lag period was unaffected by prior exposure of PMN to rTNF alpha in suspension, by allowing PMN to adhere before adding rTNF alpha, or by incubating adherent PMN in medium conditioned by rTNF alpha-treated PMN. Cytochalasins abolished H2O2 secretion in response to rTNFs, but not FMLP, if added during, but not after, the lag period. Thus, H2O2 secretion from rTNF alpha-treated PMN appears to be a direct but delayed response that requires assembly of microfilaments during exposure to the cytokine. These results suggest that PMN adherent to intra- or extravascular surfaces may undergo a massive, prolonged respiratory burst at the command of macrophages and lymphocytes reacting to microbial products and antigens.
 ...
PMID:Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes. 244 80

Interferon or 2'-5' oligoadenylates (2'-5' An) activated the microbicidal activity of primary cultures of rat glia cells and of the mouse macrophage transformed cell line J774 against infection by Trypanosoma cruzi. Pretreatment with gamma-interferon (gamma-IFN) or 2'-5' A3 of rat glia cells or direct addition of these compounds during the incubation with the parasite enhanced the uptake of metacyclic trypanosomes by the cells. Furthermore, glia cells treated with gamma-IFN or 2'-5' A3 were able to restrict the growth and to eventually destroy intracellular amastigotes. Bacterial lipopolysaccharide (LPS) synergized with gamma-IFN as well as with 2'-5' A3 and 2'-5' A4, but not with dephosphorylated 'core' molecules or ATP, to induce a partial trypanocidal activity in J774 cells. In addition, those treatments with gamma-IFN or 2'-5' A3 activated to a similar extent an endoribonuclease, which degraded ribosomal RNA, in rat glia cells, suggesting a role of this enzyme in the mechanism of the trypanocidal activity of gamma-IFN.
 ...
PMID:Stimulation of the trypanocidal and endoribonuclease activities by the interferon induced (2'-5') oligoadenylates. 244 17

Interferon-gamma (IFN-gamma) has been shown to be a potent inducer of neopterin secretion by human peripheral blood monocytes/macrophages (1). In this paper, it is shown that other known stimuli of monocytes (e.g., to secrete proteases or to migrate) such as zymosan-activated human serum, lipopolysaccharide, human C3/iC3 and zymosan coated with complement were unable to trigger monocytes/macrophages to release neopterin. Monocytes/macrophages could be stimulated solely by IFN-gamma (25 U/ml) and IFN-alpha at very high concentrations (10,000 U/ml). In the case of human peripheral blood mononuclear cells (PBMNC), basically the same pattern was observed. If however, in the buffer controls PBMNC showed some neopterin release, all stimuli triggered an increase of neopterin secretion: 10,000 U/ml IFN-alpha induced the same amount of secreted neopterin as did 25 U/ml of IFN-gamma. Both caused higher levels of neopterin secretion than ZAS, LPS and C3/iC3. Amongst the supernatants from PBMNC, only those which were obtained from cells activated with IFN-gamma or -alpha stimulated monocytes/macrophages to produce neopterin. Supernatants from lymphocytes activated with zymosan, lipopolysaccharide and interferon did not contain neopterin, nor did the latter induce monocytes/macrophages to generate and secrete neopterin. Antibodies against IFN-gamma inhibited the triggering effect of the supernatants except when generated by IFN-alpha at 10,000 U/ml. These results demonstrate that both interferons, IFN-gamma and IFN-alpha, the latter only at a 400-fold higher concentration, can trigger monocytes/macrophages directly to secrete neopterin. ZAS, LPS and C3/iC3 are weakly effective only on a mixture of lymphocytes and monocytes/macrophages, provided this cell mixture shows already a basic spontaneous neopterin release.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Selective induction of mononuclear phagocytes to produce neopterin by interferons. 245 28

When various synthetic double- or single-stranded DNAs were incubated with spleen cells from mice (BALB/c or CDF1) at 37 degrees for 20 hr, it was found that some of the DNAs augmented NK activity and produced factors in the culture supernatants which showed antiviral activity and activity to render mouse macrophages cytotoxic toward tumor cells. Poly(dG,dC) showed the strongest activities, when incubated with spleen cells from lipopolysaccharide-nonresponsive mice, C3H/HeJ. The activity of the culture supernatant to activate macrophages was completely abolished by a small amount of anti-IFN gamma antibody. On the other hand, the virus-inhibitory activity of the supernatant was mostly neutralized by anti-IFN alpha/beta. When IMC tumor cells (5 x 10(5) cells) were mixed with poly(dG,dC) (100 micrograms) and then inoculated intradermally into CDF1 mice, the tumor did not take, while tumors grew progressively and killed the mice in a control group inoculated with tumor cells alone. Direct cytotoxicity of poly(dG,dC) at a concentration of 1,000 micrograms/ml against IMC cells was not observed in vitro.
 ...
PMID:A synthetic single-stranded DNA, poly(dG,dC), induces interferon-alpha/beta and -gamma, augments natural killer activity, and suppresses tumor growth. 245 72

Injection of syngeneic lymphoma cells in AKR mice, resulted in an important increase of splenic natural killer (NK) activity in the early days following the graft. Modifications of the production of different types of cytokine: interferon, interleukins 1 and 2, tumor necrosis factor (IFN, IL-1, IL-2, TNF), involved in the regulation of NK activity, were investigated in short-term cultures of total, adherent and non-adherent fractionated spleen cells, using lipopolysaccharide as the triggering or amplifying agent. Upon stimulation with lipopolysaccharide, splenocytes from lymphoma-grafted mice released a large amount of interferon as compared to controls with a maximum level 1 day after the graft. Equal amounts of IFN-gamma and IFN-alpha/beta were detected. Treatment of spleen cells prior to culture with anti-(asialo-GM1) or anti-(Thy-1.1) antibodies reduced interferon production by 80% and 50% respectively. This finding indicates that (a) the IFN-gamma is produced by Thy-1-positive cells and (b) the production of IFN-gamma by these cells is at least partially under the control of asialo-GM1-positive cells. We also showed that non-adherent fractionated spleen cells from lymphoma-grafted mice produced IL-1 and IL-2. IL-1 was released by asialo-GM1-positive cells and IL-2 by Thy-1-positive cells. Adherent cells released only IL-1. In contrast, total cells released smaller amounts of IL-1 and IL-2, suggesting a reciprocal inhibition between subpopulations of non-adherent and adherent cells. A high level of TNF production by adherent cells was observed only 4 days after the graft. These results indicate that graft of lymphoma cells entails important modifications of spleen cell populations releasing different types of cytokines implicated in NK activation.
 ...
PMID:Production of cytokines after lipopolysaccharide stimulation of murine spleen cells during lymphoma development in AKR mice. 246 13

The cytokine IFN beta 2/IL-6 has recently been shown to regulate the expression of genes encoding hepatic acute phase plasma proteins. INF beta 2/IL-6 has also been shown to be identical to MGI-2, a protein that induces differentiation of bone marrow precursor cells toward mature granulocytes and monocytes. Accordingly, we have examined the effect of IFN beta 2/IL-6 on expression of the IL-1- and tumor necrosis factor-unresponsive acute phase protein alpha 1-antitrypsin (alpha 1 AT) in human hepatoma-derived hepatocytes and in human mononuclear phagocytes. Purified human fibroblast and recombinant IFN beta 2/IL-6 each mediate a specific increase in steady-state levels of alpha 1 AT mRNA and a corresponding increase in net synthesis of alpha 1 AT in primary cultures of human peripheral blood monocytes as well as in HepG2 and Hep3B cells. Thus, the effect of IFN beta 2/IL-6 on alpha 1 AT gene expression in these cells is primarily due to an increase in accumulation of alpha 1 AT mRNA and can be distinguished from the direct, predominantly translational effect of bacterial lipopolysaccharide on expression of this gene in monocytes and macrophages. The results indicate that IFN beta 2/IL-6 regulates acute phase gene expression, specifically alpha 1 AT gene expression, in extrahepatic as well as hepatic cell types.
 ...
PMID:Interferon beta 2/interleukin 6 modulates synthesis of alpha 1-antitrypsin in human mononuclear phagocytes and in human hepatoma cells. 247 25

Studies indicate that, among a number of other cytokines, interferons (IFN alpha, beta and gamma) are important elements regulating acute as well as chronic inflammatory responses. The role of interferons has been investigated in various experimental models of inflammation, by administration both of interferons and of antibodies that block the biological activity of interferons formed endogenously. The conclusions reached from these experiments clearly indicate that interferons can boost as well as inhibit inflammation. The effects depend on the type of inflammation studied, the time of interferon administration or emergence in the tissue, the type of interferon (alpha/beta or gamma), the dosage, and the presence of other inflammation-controlling cytokines. The effect of blockage of IFN gamma by the systemic administration of neutralising antibodies is particularly clear. Such blockage has been found to profoundly modify local lipopolysaccharide (LPS)-induced inflammation, brain inflammation due to autoimmunity or infection, and shock reactions caused by systemic administration of LPS. Further research on the particular place occupied by interferons in the inflammation-controlling cytokine network holds great promise, not only for better understanding but also for improved therapy of acute and chronic inflammatory disease.
 ...
PMID:The potential role of interferons and interferon antagonists in inflammatory disease. 248 67

T-cell activation is dependent on nominal antigen associated with major histocompatibility complex (MHC) class II molecules and interleukin-1 (IL-1), both provided by antigen-presenting cells. We have studied the effects of Brucella abortus and recombinant bovine gamma interferon (IFN-gamma) on bovine macrophage expression of MHC class II and IL-1 molecules and subsequent T-cell proliferation in response to B. abortus. When peripheral blood mononuclear cells were cocultured with B. abortus and IFN-gamma, increasing amounts of IFN-gamma, from 1 to 100 U/ml, down regulated T-cell proliferation. Expression of MHC class II molecules on macrophages was increased independently by IFN-gamma or B. abortus treatment. Thus, class II molecule expression was not the cause of down regulation of T-cell proliferation as observed in other systems. However, B. abortus-IFN-gamma-treated macrophages obtained from overnight cultures had minimal membrane IL-1 compared with macrophages treated with B. abortus alone. Loss of membrane IL-1 required IFN-gamma and the o-polysaccharide of the lipopolysaccharide. IFN-gamma at 1 U/ml in combination with B. abortus produced a 32% decrease in T-cell response, while IFN-gamma at 100 U/ml added to B. abortus-treated cultures produced an 82% reduction in T-cell response. Membrane IL-1 levels were not altered when recombinant bovine IFN-alpha or the rough strain 45/20 of B. abortus, which lacks the o-polysaccharide, was used. Secreted IL-1 levels were unaffected by IFN-gamma and B. abortus treatment. The addition of recombinant bovine IL-1 beta (0.001 to 0.1 ng/ml) to B. abortus- and IFN-gamma-treated cultures failed to provide a signal necessary for T-cell proliferation. These data suggest that membrane IL-1 has a key role in T-cell activation in response to B. abortus. When the o-polysaccharide of B. abortus lipopolysaccharide is combined with IFN-gamma at an inappropriate time during an immune response, T-cell proliferation is prevented and cannot be restored by the addition of exogenous IL-1.
 ...
PMID:Brucella abortus regulates bovine macrophage-T-cell interaction by major histocompatibility complex class II and interleukin-1 expression. 249 12


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