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)

The expression and function of a new cytokine-induced endothelial cell adhesion protein, vascular cell adhesion molecule-1 (VCAM-1), was characterized in vitro by using a monoclonal antibody, MoAb 4B9, which recognizes a functional epitope on this protein. As determined by enzyme-linked immunosorbent assay and radioimmunoprecipitation of metabolically labeled cells, VCAM-1 was minimally expressed on unstimulated human umbilical vein endothelium (HUVE), but was rapidly induced by recombinant human tumor necrosis factor-alpha (rhTNF-alpha), rh interleukin-1, and lipopolysaccharide. In contrast to intercellular adhesion molecule-1, VCAM-1 was not induced on dermal fibroblasts or arterial smooth muscle cells after stimulation with rhTNF, or on keratinocytes after stimulation with rh interferon-gamma. MoAb 4B9 significantly inhibited the adherence of peripheral blood lymphocytes (PBL) and lymphocytic cell lines, but not neutrophils, to rhTNF-activated HUVE. The inhibitory effect of MoAb 4B9 on PBL adherence to HUVE was additive to that produced by the CD18 MoAb 60.3. These results show that VCAM-1 mediates a CD18-independent pathway of peripheral blood lymphocyte adherence to cytokine-stimulated HUVE. We propose that lymphocyte binding to VCAM-1, induced on endothelium by cytokines, may be an important component of lymphocyte emigration at sites of inflammation or immune reaction.
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PMID:Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. 169 86

The present study investigates the potential capacity of the immunostimulant Corynebacterium parvum (C.p.) to induce tumor necrosis factor-alpha (TNF-alpha) in human peripheral blood mononuclear cells (PBMC) and blood monocytes (BMo) in vitro. Both at the mRNA and protein level, stimulation of PBMC and BMo upon C.p. induces TNF-alpha. Compared to the hitherto used TNF-alpha inducers in vitro such as Sendai virus, phytohemagglutinin or lipopolysaccharide the C.p. stimulus displayed a threefold stronger induction of TNF-alpha production (p less than 0.001). Using C.p. as an inducer it was possible to demonstrate that TNF-alpha production is regulated by prostaglandin E2; preincubation of the cells with prostaglandin E2 resulted in a reduced C.p.-mediated TNF-alpha production (p less than 0.001). Coincubation of interferon-gamma (IFN-gamma) together with C.p. led to an enhanced release of TNF-alpha, supporting the assumption that C.p. is a potent TNF-alpha inducer. The additive effect of IFN-gamma and TNF-alpha on the receptor level was demonstrated by addition of IFN-gamma antibodies to the PBMC cultures. Under these conditions TNF-alpha production, stimulated by C.p. and IFN-gamma, was decreased by 30%, compared to the production in assays supplemented with C.p. alone. From these data we conclude that C.p. is a new inducer of TNF-alpha in vitro and a useful tool to study TNF-alpha production of PBMC and BMo from either healthy donors or from patients.
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PMID:Corynebacterium parvum (Propionibacterium acnes): an inducer of tumor necrosis factor-alpha in human peripheral blood mononuclear cells and monocytes in vitro. 169 32

In this report we have analyzed the effect of recombinant interleukin 2 (rIL 2) and rIL 2-activated natural killer (NK) cells on the production of immunoglobulin isotypes by lipopolysaccharide (LPS)-stimulated spleen cells from nude mice. We found that rIL 2 induced a dose-dependent increase of IgG2a secretion and a concomitant inhibition of the secretion of other Ig isotypes. The analysis of the phenotype of LPS- and LPS+ rIL 2-stimulated nude spleen cells showed the appearance of a Thy-1+ asialo GM-1+slgM-CD3-CD4-CD8- cell population in the presence of rIL 2. A population with a similar phenotype was generated upon stimulation of spleen cells from nude mice with rIL 2 alone. These cells lysed YAC-1 cells, did not contain the alpha or gamma transcripts encoding the corresponding T cell receptor chains and are therefore NK cells activated by rIL 2. In co-culture experiments, these cells selectively increased the secretion of IgG2a by LPS-stimulated splenocytes from nude mice. The IgG2a induction triggered by rIL 2-activated NK cells, as well as that triggered by rIL 2, were blocked by an anti-interferon gamma monoclonal antibody. Thus, rIL 2 activated-NK cells enhance the production of IgG2a by secreting interferon-gamma.
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PMID:Recombinant interleukin 2-activated natural killer cells regulate IgG2a production. 169 33

Vascular endothelial cells contain a constitutive nitric oxide (NO) synthase that is Ca2(+)-dependent. In addition, we have found that these cells express, after activation with interferon-gamma and lipopolysaccharide, an inducible Ca2(+)-independent NO synthase that is distinct from the constitutive enzyme. The generation of NO by this enzyme was detectable after a lag period of 2 hr, reached a maximum between 6 and 12 hr, and was maintained for the duration of the experiment (48 hr). The expression of the inducible NO synthase was inhibited by the protein synthesis inhibitor cycloheximide, a compound that had no direct effect on the activity of either of the two enzymes. Furthermore, hydrocortisone and dexamethasone, but not progesterone, inhibited the expression of the inducible enzyme, without directly affecting the activity of either enzyme, without directly affecting the activity of either enzyme. The effect of these steroids was inhibited in a concentration-dependent manner by cortexolone, a partial agonist of glucocorticoid receptors. Thus, the inhibition of the induction of an NO synthase by glucocorticoids is a receptor-mediated event involving the inhibition of the synthesis of mRNA for de novo synthesis of this enzyme. The induction of this NO synthase may contribute to the pathophysiology of immunologically based conditions. Furthermore, the inhibition of this induction by anti-inflammatory steroids may explain some of the therapeutic and adverse effects of these compounds.
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PMID:Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. 170 14

The versatility and importance of macrophages in host defense and homeostasis have long been recognized. Anatomically, macrophages isolated from various tissues manifest extreme differences in shape, in metabolic and functional activities, and in the expression of macrophage-specific markers. To determine the mechanisms responsible for generating macrophage heterogeneity, we have employed the reverse transcription-polymerase chain reaction to molecularly phenotype colonies of bone marrow-derived macrophages during differentiation in vitro. By utilizing this method, results have revealed a hierarchal expression of macrophage-associated genes. Tumor necrosis factor alpha was expressed in all colonies analyzed suggesting an important role for this molecule during macrophage differentiation. Predominant colony phenotypes observed were unique for (i) the period of differentiation and (ii) the growth factor with which they were derived (either colony-stimulating factor 1 or granulocyte-macrophage colony-stimulating factor). Exogenous stimulation of the cultures with either bacterial lipopolysaccharide or interferon-gamma led to predictable phenotypic transitions. These results suggest that macrophage heterogeneity is generated through differentiation-related mechanisms and that generated macrophage phenotypes are then maintained by systemic environmental constraints.
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PMID:Macrophage heterogeneity occurs through a developmental mechanism. 170 15

Alpha-1-antitrypsin (AT) is one of several alpha-globulins which have been shown to be inhibitors of human peripheral blood monocyte TNF secretion in vitro. AT deficiency states exist, within which individuals of either the PiSS or PiZZ phenotype have reduced hepatocyte and mononuclear phagocyte AT secretion when compared to normal PiMM subjects. Here we have compared the capacity of peripheral blood monocytes of all three phenotypes to respond to both enhancers and inhibitors of TNF secretion. All monocytes exposed to lipopolysaccharide (LPS), interferon-gamma (IFN-gamma) and endotoxin, PGE2, transforming growth factor-beta 1, whole plasma alpha-globulins, purified AT and IL-6 responded equally with respect to the secretion of TNF. Our findings show that the regulation of TNF secretion in leukocytes from AT deficient humans is normal and suggest that defective AT secretion alone does not result in the aberrant regulation of TNF secretion.
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PMID:Regulation of tumor necrosis factor secretion in leukocytes from alpha-1-antitrypsin deficient humans. 170 19

Endothelial leucocyte adhesion molecule-1 (ELAM-1) is a recently described endothelial surface glycoprotein which is inducible by interleukin 1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) or bacterial lipopolysaccharide (LPS). Using an immunohistochemical technique and a monoclonal antibody (1.2B6) specific for ELAM-1 we have found marked vascular endothelial expression of ELAM-1 in many cutaneous inflammatory disorders, including allergic contact dermatitis, atopic dermatitis and psoriasis, and in dermal infiltrates associated with benign, premalignant and malignant keratinocyte proliferation. In normal skin, minimal levels of ELAM-1 expression were detected. In psoriasis, double-immunoenzyme staining studies revealed a close spatial relationship between ELAM-1 expression and neutrophil margination, suggesting a functional link. Recombinant human interferon-gamma (30 micrograms) injected intradermally in normal adult human volunteers did not substantially upregulate ELAM-1 in contrast to its marked effect on intercellular adhesion molecule-1 (ICAM-1) expression, indicating that this cytokine is probably not involved in ELAM-1 induction in vivo. These results indicate that ELAM-1 is widely induced in cutaneous inflammation with a time course of expression that is longer than that observed in vitro. As ELAM-1 acts as an adhesion ligand for neutrophils, and perhaps monocytes, the expression of this molecule in cutaneous lesions is likely to be an indication of the ability of vascular endothelium to recruit these cells from the circulation. Furthermore, the cytokine inducibility of ELAM-1 is indirect evidence for functional interactions between perivascular mononuclear cells, other resident cells and the blood vessel wall.
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PMID:Endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in cutaneous inflammation. 170 95

An adherent cell line was established from the much studied pre-B cell line 70Z/3. The adherent cell line had the morphological features of a macrophage and stained positive for non-specific esterase. In addition, this line expressed high levels of RNA for the macrophage specific enzyme, lysozyme. Although the 70Z/3 macrophage variant has lost the ability to respond to lipopolysaccharide and interferon-gamma by expressing RNA transcripts for immunoglobulin light chain, it exhibited a new response characterized by increased levels of I-A RNA transcripts. Both the pre-B and macrophage variants also expressed RNA transcripts which hybridize to a Hox 2.3 probe. In contrast, transcripts which hybridize to Hox 1.1, 2.1, and 6.1 probes are expressed in the pre-B line but could not be detected in the macrophage.
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PMID:Characterization of a 70Z/3 pre-B cell derived macrophage clone. Differential expression of Hox family genes. 170 3

The cytosol fraction of J774-1 murine macrophages activated with lipopolysaccharide (LPS) + interferon-gamma (IFN-gamma) was found to nitrosate a wide range of secondary and tertiary amines. The reaction was dependent on L-arginine and NADPH. The optimal pH for nitrosation was 7.2-7.3. Nitrosation was inhibited by arginine derivatives such as NG-monomethyl-L-arginine and NG-nitro-L-arginine, well-known inhibitors of nitric oxide (NO) synthase. These results indicate that nitrosation is mediated by NO synthase, which catalyzes formation of NO and L-citrulline from L-arginine. Nitrosamine formation also required oxygen and was inversely correlated with the basicity of nitrosatable amines. The nitrosation was inhibited by oxyhemoglobin, an NO trapping agent, and enhanced by superoxide dismutase, which stabilizes NO. LPS + IFN-gamma induced approximately 500-600 times greater nitrosation activity than that of non-activated macrophages. Macrophages treated with LPS alone exhibited 3-4 times greater nitrosation activity than untreated macrophages, whereas macrophages treated with IFN-gamma alone did not show enhanced nitrosation activity. A combination of the cytosols from macrophages treated with LPS alone and IFN-gamma alone did not nitrosate morpholine as rapidly as the cytosol of macrophages treated with both compounds together. The activity for forming L-citrulline and nitrite/nitrate from L-arginine was markedly induced by treatment with either LPS alone or LPS + IFN-gamma but not with IFN-gamma. Those results suggest that some other factor(s) in addition to NO synthase is involved for efficient nitrosation by the macrophage cytosol. This factor(s) was not induced in macrophages by either LPS- or IFN-gamma alone, but was induced only in the presence of the two compounds.
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PMID:L-arginine-dependent formation of N-nitrosamines by the cytosol of macrophages activated with lipopolysaccharide and interferon-gamma. 171 76

Intravenous (IV) administration of purified lipopolysaccharide (LPS) from Salmonella abortus equi to cancer patients induces the formation of high amounts of endogenous cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). On repeated administration of LPS at 2-week intervals, a marked downregulation of the cytokine response was observed, especially between the first and the second challenge. This study sought to determine whether it would be possible to prevent this downregulation by pretreating patients with interferon-gamma (IFN-gamma), which is known to enhance cytokine production by monocytes and macrophages in vitro. Ten patients with disseminated cancer received a first injection of 4.0 ng LPS/kg. Thereafter, patients were divided into two groups. One group received two further LPS injections (4.0 ng/kg) at 2-week intervals. The second group was pretreated (-12 hours) with 50 micrograms IFN-gamma subcutaneously (SC) before the second and third LPS challenge. To prevent constitutional side effects such as fever and chills, patients received 1,600 mg ibuprofen orally before LPS injection. The results of the current study demonstrate that apart from TNF-alpha and IL-6, two other cytokines, interleukin-8 (IL-8) and granulocyte colony-stimulating factor (G-CSF) are produced in cancer patients in response to LPS. LPS application at 2-week intervals resulted in a transient attenuation of all cytokines (TNF-alpha, IL-6, IL-8, G-CSF) on the second challenge. In the case of TNF-alpha, IL-6, and G-CSF, pretreatment with IFN-gamma not only prevented the downregulation, but enhanced the production of these cytokines to levels higher than those obtained after the first LPS challenge. In contrast, the downregulation of IL-8 remained unaffected by IFN-gamma pretreatment. Further studies are warranted to determine whether the prevention of cytokine downregulation by IFN-gamma following repeated LPS injections is of clinical relevance in respect to the antitumor activity of LPS.
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PMID:Modulating activity of interferon-gamma on endotoxin-induced cytokine production in cancer patients. 172 Jul 1


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