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)

Tumor necrosis factor (TNF) is a cytokine released predominantly by monocytes/macrophages that has been shown to modulate a variety of different immune and metabolic functions. To understand the regulatory mechanisms of TNF in governing responses in the pleural cavity following deposition of fibrous dust in the airspace of the lung, we studied the capability of leukocytes, lavaged from the pleural cavity, to release TNF in culture. TNF production by lavaged pleural leukocytes was measured using the L-929 TNF-sensitive cell line, after intratracheal instillation of crocidolite asbestos. A high level of TNF activity was found in the supernatants of normal, unstimulated pleural leukocytes; the addition of 100 ng/ml lipopolysaccharide to the culture increased the activity up to threefold. Following intratracheal instillation of 5 mg crocidolite asbestos, the pleural leukocytes secreted less TNF than the control. With increasing mass of intratracheally instilled asbestos, there was a dose-dependent reduction in TNF release. Changes in the population of the pleural leukocytes or their number could not be related to variation in TNF activity. These results suggest that exposure of rat lungs to crocidolite asbestos by intratracheal instillation affects the response of pleural leukocytes without causing changes in the population. Such changes in the bronchoalveolar space may be related to the pleural pathology found in asbestos-exposed individuals.
 ...
PMID:Intratracheal injection of crocidolite asbestos depresses the secretion of tumor necrosis factor by pleural leukocytes in vitro. 162 68

Superoxide (O2-) and granulocyte elastase (GE) from neutrophils mediate host defense and tissue injury in inflammation. To determine alterations in leukocyte function after trauma, O2- production and GE secretion from neutrophils were studied in trauma patients (n = 20) and healthy controls (n = 15). The priming effect of tumor necrosis factor (TNF), interleukin-1 alpha (IL-1 alpha), and lipopolysaccharide (LPS) on O2- or GE release also was evaluated. Superoxide production (nmole/10 minutes) was elevated significantly in trauma patients at days 0 (9.5 +/- 4.8), 1 (14.2 +/- 7.3), and 3 (12.2 +/- 5.9) and returned to control levels (4.2 +/- 1.6) by day 7. There was no difference in GE secretion between trauma patients and healthy controls. Incubation of neutrophils with TNF induced release of both O2- and GE. Superoxide production was induced by TNF at concentrations at or greater than 10(-11) mol/L. Granulocyte elastase secretion was induced in a time- and dose-dependent manner by TNF at concentrations between 10(-10) and 10(-7) mol/L. In contrast IL-1 alpha and LPS did not potentiate O2- or GE release. These results suggest that neutrophil O2- production increases acutely in trauma. Tumor necrosis factor may mediate this O2- and GE production by neutrophils involved in the inflammatory response.
 ...
PMID:Acceleration of superoxide production from leukocytes in trauma patients. 165 Oct 73

Lead markedly augments the lethality of endotoxin lipopolysaccharide (LPS) in rats. In this model of LPS toxicity, the liver is severely injured. Much of the tissue injury produced by LPS is thought to be mediated by the cytokine tumor necrosis factor (TNF). Tumor necrosis factor recently has been speculated to be a mediator of several models of liver injury such as that produced by galactosamine. To investigate the possible role of TNF in the lead-enhanced LPS toxicity model, we administered doses of lead acetate (15 mg/kg), LPS (100 micrograms/kg), or TNF (6.25 x 10(6) U/kg) that produced minimal changes in liver enzymes. However, when lead was administered simultaneously with either LPS or TNF, serum aspartate transaminase, alanine transaminase, alkaline phosphatase, glutamyl transpeptidase, and plasma triglyceride levels were markedly increased. Lead + LPS treatment increased both peak serum TNF concentrations and TNF "area under the curve" as compared with LPS alone. We conclude that lead not only enhances LPS lethality but also LPS liver injury. Furthermore, lead enhances TNF liver injury and increases LPS-stimulated serum TNF levels. These data suggest that the lead-enhanced LPS model offers a system for studying TNF-induced liver injury.
 ...
PMID:Lead enhances lipopolysaccharide and tumor necrosis factor liver injury. 167 39

Tumor necrosis factor (TNF) is a cytokine which stimulates osteoclastic bone resorption and inhibits collagen synthesis in vitro. In this study the effect of human cholesteatoma debris and its constituents on the production of TNF-alpha by human monocytes in vitro was studied. Cultured human peripheral monocytes secreted TNF into the culture medium when exposed to cholesteatoma debris in a dose-dependent manner. The TNF production, however, was partially inhibited by the treatment of the debris with polymyxin B which inhibits biological activities of lipopolysaccharide (LPS). When individual constituents of cholesteatoma debris, i.e. keratin, cholesterol, lauric acid and LPS, were added to the cultured monocytes at concentrations equivalent to those in the debris, significant production of TNF was observed only with the keratin and LPS. These data suggest that cholesteatoma debris is a potent activator of the TNF production of human monocytes in vitro, and that LPS and keratin are responsible for the production.
 ...
PMID:Cholesteatoma debris as an activator of human monocytes. Potentiation of the production of tumor necrosis factor. 170 75

Tumor necrosis factor plays a central role in the mediation of the pathophysiological sequelae of infection and inflammation in animals and humans. The elucidation of its role in respiratory disease of swine has not been investigated, due in part to the lack of a sensitive and specific quantitative assay for its presence in tissue and fluid samples. Here we describe the detection of porcine tumor necrosis factor utilizing L929 murine fibroblast cells and characterize various parameters affecting assay sensitivity. Plating cell density and length of exposure time to test supernatants were the most critical factors. Using standard assay conditions as described here, porcine tumor necrosis factor was detected in alveolar macrophage conditioned media diluted more than 400-fold. Specificity of the assay for porcine tumor necrosis factor was shown by inhibition of cytotoxicity with neutralizing polyclonal antibodies for human recombinant tumor necrosis factor. Furthermore, comparisons of bioactivity with tumor necrosis factor mRNA levels from lipopolysaccharide-stimulated porcine alveolar macrophages indicated that the L929 bioassay was specific for porcine tumor necrosis factor.
 ...
PMID:Detection of tumor necrosis factor alpha from porcine alveolar macrophages using an L929 fibroblast bioassay. 171 31

Tumor necrosis factor-alpha (TNF-alpha), which is produced mainly by monocyte/macrophage cells, has diverse physiological functions on lymphoid cells. Moreover, it has been shown that TNF-alpha exhibits antiviral activities. Here we report that Epstein-Barr virus (EBV), a B lymphotropic human herpes virus that interacts intimately with the immune system, exerts a strong inhibitory effect on TNF-alpha production by lipopolysaccharide-treated peripheral blood leukocytes as well as by monocytic cell lines, HL-60 and U-937. Flow cytometric analysis following staining with OKB7 monoclonal antibody showed that about 20% of cells from these monocytic lines express the CR2 antigen. Direct binding of fluorescein isothiocyanate-labeled EBV indicated that the virus binds to approximately 22% of cells of both monocytic lines. However, no virus-specific antigens were detected in the infected cells by immunofluorescence, suggesting that the infection was of the abortive type. The use of UV- or heat-inactivated EBV and inhibitory effect on TNF-alpha synthesis. These results suggest that infectious virus is necessary to obtain such an inhibitory effect. Analysis of TNF-alpha mRNA by polymerase chain reaction amplification indicated that the EBV suppressive effect is manifested at the transcriptional level. In contrast, EBV did not inhibit interleukin 1 mRNA production by these cells. These results indicate that EBV interacts directly with monocytes/macrophages to exert its immunomodulatory effect.
 ...
PMID:Inhibition of tumor necrosis factor-alpha transcription by Epstein-Barr virus. 184 16

Purified capsular polysaccharide (CPS) stimulated significant release of interleukin-1 (IL-1) activity from bovine blood monocytes but not alveolar macrophages in vitro. The ability of CPS to induce IL-1 release was resistant to boiling and inhibited by the addition of polymyxin beta. Thus, it is likely that the IL-1 release stimulated by CPS resulted from the small amount of contaminating lipopolysaccharide (LPS) that was present (an estimated 5 pg LPS per microgram CPS) rather than to a direct effect of CPS. Tumor necrosis factor activity was not detected in the culture supernatants of bovine monocytes incubated with purified CPS for 1-18 h in vitro.
 ...
PMID:Pasteurella haemolytica A1 purified capsular polysaccharide does not stimulate interleukin-1 and tumor necrosis factor release by bovine monocytes and alveolar macrophages. 186 93

Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease. 189 44

Protein phosphorylation is central to multiple regulatory processes in cells. Tumor necrosis factor (TNF), a cytokine synthesized by macrophages, effects polymorphonuclear leukocyte (neutrophil) chemotaxis, induces superoxide anion generation, and mediates neutrophil adhesion to endothelial cells. Although protein phosphorylation is almost certainly involved in many TNF-mediated neutrophil functions, little is known about TNF's impact on neutrophil protein phosphorylation. Therefore, we studied human recombinant TNF-alpha-induced protein phosphorylation in human neutrophils. Neutrophils were preincubated with 32PO(4)2- and treated with a variety of stimulatory agents. One- and two-dimensional polyacrylamide gel electrophoresis was used to analyze phosphorylated proteins. Phosphoaminoacids were identified by two-dimensional thin layer chromatography electrophoresis. The findings were as follows: (1) TNF induces the phosphorylation of two 16-kD proteins (pI = 5.9 and 6.1) by 5- to 6-fold, and a 57-kD protein (pI = 5.8) by 3- to 4-fold compared with untreated neutrophils; (2) these proteins are phosphorylated as early as 15 min after stimulation with TNF, and phosphorylation is induced by concentrations of TNF as low as 1 ng/ml (10 U/ml); (3) TNF induces the phosphorylation of proteins at either serine or threonine residues and not at tyrosine; (4) TNF-stimulated neutrophils show a unique pattern of protein phosphorylation when compared to neutrophils treated with formylmethionylleucylphenylalanine; (5) lipopolysaccharide does not induce protein phosphorylation in neutrophils; (6) a 16-kD protein is phosphorylated in response to TNF in neutrophils but not in mononuclear cells; and (7) protein kinase inhibitors appear to have no effect on TNF-induced protein phosphorylation. Thus, the mechanism of action of TNF on neutrophils may involve protein phosphorylation.
 ...
PMID:Tumor necrosis factor-induced protein phosphorylation in human neutrophils. 191 Aug 14

The present study was designed to investigate the capacity of human vascular smooth muscle cells (SMCs) to produce a cytokine chemotactic for monocytes (monocyte chemotactic protein [MCP]) and by way of comparison, a related polypeptide activator of neutrophils (known as interleukin-8 [IL-8] or neutrophil activating protein-1 [NAP-1]. On exposure to IL-1, SMCs released high levels of chemotactic activity for monocytes, which could be removed by absorption with anti-MCP antibodies. MCP production by activated SMCs was comparable to that of IL-1-stimulated umbilical vein endothelial cells. Activated SMCs released appreciable levels of IL-8, as determined by a specific enzyme-linked immunosorbent assay, but little chemotactic activity for neutrophils. IL-1-treated SMCs expressed high levels of both MCP and IL-8 mRNA transcripts, as assessed by Northern blot analysis. Tumor necrosis factor and bacterial lipopolysaccharide but not IL-6 also induced MCP and IL-8 gene expression in SMCs. Nuclear runoff analysis revealed that IL-1 augmented transcription of the MCP and IL-8 genes. The capacity of SMCs to produce a cytokine (MCP) that recruits and activates circulating mononuclear phagocytes may be of considerable importance in the pathogenesis of vascular diseases (e.g., vasculitis and atherosclerosis) that are characterized by monocyte infiltration of the vessel wall.
 ...
PMID:Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells. 191 3


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