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

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.
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PMID:Inhibitory versus stimulatory effects of natural human interferon-alpha on proliferation of lymphocyte subpopulations. 153 94

The influence of cytokines on extracellular superoxide dismutase (EC-SOD) expression by human dermal fibroblasts was investigated. The expression was markedly stimulated by interferon-gamma (IFN-gamma), was varying between fibroblast lines stimulated or depressed by interleukin-1 alpha (IL-1 alpha), was intermediately depressed by tumor necrosis factor-alpha (TNF-alpha), and markedly depressed by transforming growth factor-beta (TGF-beta). TNF-alpha, however, enhanced the stimulation by a high dose of IFN-gamma, whereas TGF-beta markedly depressed the stimulations given by IFN-gamma and IL-1 alpha. The ratio between the maximal stimulation and depression observed was around 30-fold. The responses were generally slow and developed over periods of several days. There were no effects of IFN-alpha, IL-2, IL-3, IL-4, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, human growth hormone, Escherichia coli lipopolysaccharide, leukotriene B4, prostaglandin E2, formylmethionylleucylphenylalanine, platelet-activating factor, and indomethacin. The cytokines influencing the EC-SOD expression are also known to influence superoxide production by leukocytes and other cell types, and the EC-SOD response pattern is roughly compatible with the notion that its function is to protect cells against extracellular superoxide radicals. The results show that EC-SOD is a participant in the complex inflammatory response orchestrated by cytokines. The CuZn-SOD activity of the fibroblasts was not influenced by any of the cytokines, whereas the Mn-SOD activity was depressed by TGF-beta. TNF-alpha, IL-1 alpha, and IFN-gamma stimulated the Mn-SOD activity, as previously known, and these responses were reduced by TGF-beta. The different responses of the three SOD isoenzymes illustrate their different physiological roles.
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PMID:Regulation by cytokines of extracellular superoxide dismutase and other superoxide dismutase isoenzymes in fibroblasts. 155 78

Triggering of the CD3 molecule by in vivo injection of the hamster anti-murine CD3 monoclonal antibody 145-2C11 in adult BALB/c mice leads to massive although transient T cell activation. High levels of tumour necrosis factor (TNF), interferon-gamma (IFN-gamma), IL-2, IL-3 and IL-6 are released into the circulation 1 to 8 h after a single 10 micrograms 145-2C11 i.v. injection. This release induces an impressive self-limited physical reaction associating hypothermia, hypomotility (as assessed by actimetry), diarrhoea, piloerection and even death when high doses (a single dose of greater than 100 micrograms/mouse injection) are administered. In vivo injection of 145-2C11 to other selected mouse strains, namely NZW, CBA/J and C3H/HeJ, induced both different cytokine release patterns and sickness. 145-2C11 induced significant release of TNF and IL-2 in all four strains. At variance, IFN-gamma was only detected in BALB/c mice sera which, in terms of physical reaction (hypothermia and hypomotility) were the most affected. Higher and long-lasting circulating IL-3/GM-CSF levels were present in CBA/J sera, correlating with a later recovery. These results underline heterogeneity in the in vivo cell activation pattern among different mouse strains, when triggering T lymphocytes via the CD3/Ti molecule as compared to exclusive targeting of monocyte/macrophages by means of lipopolysaccharide.
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PMID:Inter-mouse strain differences in the in vivo anti-CD3 induced cytokine release. 172 Oct 15

Mouse macrophage BAM3 cells produced colony-stimulating factors (CSFs) after stimulation with bacterial lipopolysaccharide (LPS). By assaying the CSF using various interleukin 3-dependent cell lines, it was shown that most of the CSFs produced by BAM3 cells were granulocyte CSF (G-CSF). The granulocyte-macrophage CSF (GM-CSF) gene was also expressed in BAM3 cells after stimulation with LPS. When BAM3 cells were fused with the mouse renal adenocarcinoma cell line RAG which does not produce G-CSF, two of four hybrid cell lines constitutively produced large quantities of G-CSF. About 300 bp of the promoter region of mouse G-CSF chromosomal gene was inserted upstream of the Escherichia coli chloramphenicol acetyltransferase gene, and introduced into BAM3, RAG and hybrid cells. The G-CSF promoter was activated by stimulation with LPS, in BAM3 cells, but was inert in RAG cells. On the other hand, there was significant constitutive CAT activity in the hybrid cells.
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PMID:Constitutive production of granulocyte colony-stimulating factor by hybrids of a SV40-transformed mouse macrophage and a renal adenocarcinoma cell line. 172 85

Phagocytosis of Giardia lamblia trophozoites by cytokine-activated and non-activated bone marrow-derived macrophages was examined in vitro. Macrophages treated with recombinant interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) ingested a significantly higher number of in vitro-grown trophozoites than untreated macrophages. Maximal uptake of parasites occurred after 4 h and 6 h of incubation where 81.4% and 79.1% of macrophages were positive for trophozoites. Other cytokines tested, IL-2, IL-3, IL-4, IL-5, GM-CSF, CSF-1 and tumour necrosis factor-alpha (TNF-alpha) either alone or in combination with LPS, failed to activate macrophages to phagocytose G. lamblia. The induction of this activated macrophage anti-microbial function was achieved pharmacologically using phorbol myristate acetate (PMA) and ionophore A23187. The giardicidal activity of macrophages activated with IFN-gamma and LPS or that induced by PMA and A23187 was inhibited by H-7, indicating the role for protein kinase C in the intracellular events following activation.
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PMID:Phagocytosis of Giardia lamblia trophozoites by cytokine-activated macrophages. 173 94

Mouse macrophages infected with Trypanosoma cruzi in vitro may be activated to reduce parasite infection by interferon gamma (IFN-gamma). The addition of up to 10,000 units of IFN-gamma however, does not result in a 100% reduction of intracellular parasites. We, therefore, investigated the possibility that macrophages require an additional signal or signals to completely clear T. cruzi infection. Because the combination of IFN-gamma with lipopolysaccharide greatly enhanced macrophages ability to decrease the number of intracellular parasites, the interaction of IFN-gamma with tumor necrosis factor (TNF) was examined. TNF alone and the combination of TNF with IFN-gamma did not have a significant effect on reducing parasite numbers below that obtained with IFN-gamma alone. This was also true for lymphotoxin, a lymphokine similar to TNF in structure and function. The effect of IFN-gamma in combination with a cytokine-rich supernatant containing IL-2, IL-3, IL-4, IL-5, and IFN-gamma on macrophage clearance of the parasite was also examined. The cytokine-rich supernatant alone had no effect on reducing parasite infection of the macrophages; indeed, in some experiments the addition of the supernatant resulted in an increase in the level of parasite infection. However, 1000 units of IFN-gamma combined with the complex cytokine mixture caused a decrease in parasite infection of nearly 100% compared to that of control cultures treated with media alone. To determine which cytokine or cytokines in the supernatant were responsible for this synergistic activity, anti-cytokine antibodies were added to the supernatant prior to its addition with IFN-gamma to the cultures. Anti-IL-4 was the only antibody found to inhibit the synergism of IFN-gamma with the cytokine-rich supernatant. IL-4, however, did not significantly enhance the ability of IFN-gamma to induce macrophage clearance of the parasite, and IL-4 alone caused a slight increase in parasite infection in vitro. These results further define the role that cytokines play in T. cruzi infection of macrophages in vitro and suggest that the interaction of cytokine networks within this system is complex.
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PMID:Trypanosoma cruzi: cytokine effects on macrophage trypanocidal activity. 190 95

The immunostimulant poly(A)-poly(U) induces a rapid enhancement of circulating colony-stimulating activity (CSA) in normal mice, culminating 2 h after i.v. injection. A dose of 200 micrograms per mouse is sufficient for a maximal effect. The colonies formed in response to sera from poly(A)-poly(U)-injected mice are mainly granulocytic with few macrophages. These sera are devoid of detectable interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF), but contain large amounts of interleukin 6 (IL-6) that are perfectly correlated with circulating CSA levels. Although, in our hands, IL-6 alone induces no colony formation in the standard methylcellulose colony assay, it is nevertheless requisite for this biological activity because 1) monoclonal antibodies against IL-6 strongly diminish colony formation in response to sera from poly(A)-poly(U)-injected mice, and 2) recombinant (r)IL-6 induces colonies when tested in combination with low amounts of normal murine serum. At the concentrations used (0.3%-2.5%), the latter has no or a very slight effect alone. Low amounts of hematopoietic growth factors, that is, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), GM-CSF, or IL-3 that are almost ineffective in the absence of IL-6 can replace normal serum. Taken together, these data suggest that circulating IL-6, induced by i.v. injection of poly(A)-poly(U), promotes colony formation by interacting with serum components that might be identical with hematopoietic growth factors present in normal serum at subliminal concentrations. Finally, the involvement of lipopolysaccharide (LPS) in this phenomenon has been ruled out by the use of the low responder strain of mice (C3H/HeJ) that leads to similar results.
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PMID:Poly(A)-poly(U) induces circulating colony-stimulating activity resulting from interactions between endogeneous interleukin 6 and serum components. 205 90

Peripheral blood-derived human polymorphonuclear leukocytes (PMNL) can be induced to synthesize prostaglandin E2 (PGE2) from endogenous and exogenous arachidonic acid (AA) when exposed to agents such as human recombinant (hr) granulocyte-macrophage (GM) colony-stimulating factor (CSF), hr tumor necrosis factor-alpha, hr granulocyte (G)-CSF, lipopolysaccharide and the chemoattractant N-formyl-methionyl-leucyl-phenylalanine. Treatment of PMNL with hr macrophage (M)-CSF and interleukin 3, however, did not result in detectable PGE2 synthesis. Cytokines stimulated PGE2 production during two distinct time intervals, an early peak of PGE2 that was detectable at 20 min and a late one detectable after 4 h. Inhibition of protein synthesis by cycloheximide (CHX) had virtually no effect on the early increase of PGE2 but prevented the late increase. Late addition of CHX to cultures after stimulation with hr GM-CSF at 4 h resulted in decline of PGE2 synthesis from exogenous arachidonic acid. Treatment of PMNL with GM-CSF had direct effects on cyclooxygenase (COx). PMNL depleted from COx by acetyl salicylic acid (ASA) recovered to synthesize PGE2 following exposure to GM-CSF. Recovery from COx inhibition by ASA could be prevented by CHX.
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PMID:Cytokine-stimulation of prostaglandin synthesis from endogenous and exogenous arachidonic acids in polymorphonuclear leukocytes involving activation and new synthesis of cyclooxygenase. 212 94

To clarify which cytokines could potentially be produced by astrocytes, we have assessed the presence of mRNA for a number of cytokines in astrocyte-enriched brain cultures. The cultures were derived from neonatal murine brain and were treated with either interferon-gamma, lipopolysaccharide or tumor necrosis factor-alpha, or infected with murine cytomegalovirus. RNA was extracted at 0, 4, 24 and 48 hours post treatment. A DNA copy of total cytoplasmic RNA was synthesised and specific cDNA amplified using the polymerase chain reaction and detected by hybridization with specific probes. The following cytokines were studied: IL3, IL4, IL6, TNF alpha, TGF beta, LIF, G-CSF, M-CSF and GM-CSF. Transcripts for TGF beta, IL6, LIF and M-CSF were present constitutively but increased with stimulation, whereas transcripts for TNF alpha, IL6, GM-CSF, G-CSF and LIF were detected only after stimulation. Messenger RNA for IL3 and IL4 was not detected. The magnitude and kinetics of the induction varied according to the cytokine and the stimulus. These results indicate the possibility of intra-cerebral production of a number of cytokines that may play a role in the clearance of viral or bacterial pathogens and in the generation of neuropathology.
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PMID:Detection of cytokine mRNA in astrocyte cultures using the polymerase chain reaction. 216 30

Media conditioned by an interleukin 3 (IL-3)-producing T-cell line, STIL-3, as well as recombinant mouse IL-3 showed granulocyte/macrophage (GM) colony-stimulating activity in the semi-solid culture medium containing horse serum (HS) or bovine serum, but the activity was not apparent when fetal calf serum (FCS) was used. No such serum-dependency of GM colony formation was observed when abdominal wall conditioned medium or L-cell conditioned medium containing GM colony-stimulating factor was used. Although the levels of albumin and total protein were lower in FCS than HS, increase of FCS concentration did not affect the GM colony-stimulating activity of IL-3. Addition of bovine serum albumin (BSA) preparation to FCS, however, increased the number of GM colonies to the same level as that observed with HS. The levels of bacterial lipopolysaccharide (LPS) in sera and BSA and the effect on the bone marrow cells from LPS-nonresponsive C3H/HeJ mice indicated that the observed effect of BSA was not due to the contaminating LPS. The activity of BSA was not substituted by IL-1, IL-2, IL-4, IFN-gamma, TNF, NGF or erythropoietin. The present study suggests the presence in BSA of co-factor(s) of IL-3 in stimulating GM colony formation.
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PMID:Presence of an activity indispensable for the granulocyte/macrophage colony-stimulating activity of interleukin 3 in bovine serum albumin. 217 34


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