Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) are secreted by macrophages in response to endotoxin challenge. In addition, macrophages express receptors for both of these cytokines. Macrophage function can therefore be modulated by regulation of both cytokine production and receptor levels. We have initiated studies to investigate the effects of TNF-alpha and IL-1 alpha on macrophage function. Macrophages were obtained by in vitro differentiation of rat bone marrow cells. The biologic response to TNF-alpha and IL-1 alpha was assessed by measurement of superoxide production quantitated by the reduction of cytochrome c in response to phorbol myristate acetate. Macrophages were treated with endotoxin (LPS), TNF-alpha, and IL-1 alpha, alone and in combination. None of these agents was a primary stimulus for superoxide production. However, after treatment with endotoxin or TNF-alpha for 24 h, macrophages were primed for enhanced production of superoxide. The priming effect of LPS was due, at least in part, to endogenously produced TNF-alpha, since anti-murine TNF-alpha antibodies blocked the LPS-mediated priming by approximately 30%. IL-1 alpha did not prime macrophages, but treatment with IL-1 alpha followed by TNF-alpha or LPS resulted in enhanced superoxide production. IL-1 alpha treatment of macrophages resulted in an increase in TNF-alpha receptors, which might explain the synergistic priming of TNF-alpha and IL-1 alpha.
Am J Respir Cell Mol Biol 1992 Oct
PMID:Tumor necrosis factor-alpha and interleukin-1 alpha synergistically enhance phorbol myristate acetate-induced superoxide production by rat bone marrow-derived macrophages. 132 12

Tumor necrosis factor (TNF) is considered to play a key role in the pathogenesis of allergic disorders. We examined TNF production in human lung fragments after IgE receptor triggering at mRNA and protein levels. IgE receptor triggering was performed by sensitizing lung fragments with monoclonal human IgE and then exposing them to anti-human IgE antibody. Cytotoxic activity against L929 cells appeared in the culture supernatant of lung fragments 2 h after IgE receptor triggering and increased for up to 4 h. This cytotoxic activity was completely neutralized by anti-human TNF antibody. Northern blot analysis demonstrated that 1.8-kb TNF mRNA transcripts in sensitized lung fragments were expressed as early as 1 h after IgE receptor triggering and continued up to 4 h. Immunohistochemical analysis revealed TNF localization in tissue mast cells, alveolar macrophages, tissue macrophages, and bronchial epithelial cells. Double staining with anti-TNF antibody and alcian blue clearly identified that lung mast cells are one of the TNF-positive cell types in the pulmonary tissue. With immunoelectron microscopy, TNF immunoreactivity was detected in the rough endoplasmic reticulum and the perinuclear spaces in tissue macrophages, and in the cytosol and the perinuclear spaces in bronchial epithelial cells. In addition, IgE was detected on the cell surface of mast cells, tissue macrophages, and alveolar macrophages. These results suggest that TNF is released from mast cells and pulmonary macrophages through IgE receptor triggering and may play a key role in the allergic reaction in human airway.
Am J Respir Cell Mol Biol 1992 Oct
PMID:Human lung mast cells and pulmonary macrophages produce tumor necrosis factor-alpha in sensitized lung tissue after IgE receptor triggering. 138 77

Tumor necrosis factor (TNF) has been shown to have diverse effects on a wide variety of cell types. In the mouse adipogenic TA1 cell line, TNF completely abolishes differentiation and reverts fully differentiated fat cells into fibroblasts. This block in differentiation and its reversal is due to the rapid reduction in the expression of adipose-specific genes. This study reports that the transcription factor, CCAAT/enhancer binding protein (C/EBP), previously reported to promote the differentiation of 3T3-L1 adipocytes, is expressed in TA1 cells. During their growth in culture, the levels of C/EBP, as evidenced by its cellular levels of specific mRNA, protein, and DNA binding activity, increase dramatically when cells reach confluence and proceed to differentiate. Addition of TNF to cultured preadipocytes or fully differentiated adipocytes rapidly reduces C/EBP levels and is accompanied by the decrease in expression of adipose-specific genes. C/EBP binding sites occur in several adipose-specific genes, and here it is demonstrated that its presence in a novel adipose-specific gene, Clone 47, also referred to as FSP27, may be responsible for the strong down-regulation of the expression of the Clone 47 (FSP27) promoter-linked chloramphenicol acetyl transferase gene by TNF. This study proposes that the loss of C/EBP in response to TNF treatment may in part explain the loss of the adipocyte differentiated state.
Mol Endocrinol 1992 Jul
PMID:CCAAT/enhancer binding protein expression is rapidly extinguished in TA1 adipocyte cells treated with tumor necrosis factor. 150 26

Tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) are inflammatory cytokines produced by alveolar macrophages (AMs) and implicated in sepsis-related adult respiratory distress syndrome (ARDS). Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS. The purpose of the present study was to examine the effect of Exosurf on inflammatory cytokine secretion from AMs in vitro. AMs were obtained from normal nonsmoking adult volunteers. Secreted TNF, IL-1, IL-6, and IL-8 were measured by enzyme-linked immunoassays in 24 h culture fluids of AMs. Exosurf inhibited LPS-stimulated TNF, IL-1, and IL-6 secretion in a dose-dependent fashion. IL-8 secretion was not affected by Exosurf under these conditions. However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf. Regulation of IL-8 production may differ from TNF, IL-1, and IL-6. Unstimulated cytokine secretion was not affected by any of the tested concentrations of Exosurf. The inhibitory effect of Exosurf on endotoxin-induced cytokine secretion by human AMs suggests that Exosurf may modulate inflammatory cytokine production in the lung.
Am J Respir Cell Mol Biol 1992 Sep
PMID:Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages. 152 Apr 90

BALB/cA, DBA/2N and CDF1 (BALB/cA x DBA/2N) mice were inoculated intranasally with the Mol strain of Sendai virus (SV), and their mortality and histopathological lung lesions were compared. BALB/cA and CDF1 were resistant and DBA/2N was susceptible in terms of mortality. The lung lesions of the resistant strains were mild and focal, and limited to the bronchial regions, whereas those of the susceptible stain were severe and diffuse, extending to the alveoli. SV antigen was found mainly in the bronchial epithelium in the resistant strains, but in the susceptible strain, the antigen was found also in many alveolar epithelial cells and alveolar macrophages. SV antigen was detected in neither regenerated bronchial epithelium nor endothelial cells. Tumor necrosis factor (TNF) was detected immunohistologically in edematous perivascular regions and in some mononuclear cells infiltrating to the regions, suggesting that TNF is involved in the development of lung lesions by SV infection in the three mouse strains.
 ...
PMID:Comparative lung pathology of inbred strain of mice resistant and susceptible to Sendai virus infection. 165 Jun 2

Tumor necrosis factor, TNF, is a 17-kDa protein secreted by macrophages and classified as a cytokine. TNF binds to high-affinity receptors on the cell surface and is involved in a wide variety of biological responses. There are at least two types of receptors, tumor necrosis factor receptors 1 and 2 (TNFR1 and TNFR2). The genes for TNFR1 a 55-kDa protein, and TNFR2, a 70-kDa protein, have been mapped to human chromosomes 1 12 (12pter-cen) and (1pter-p32), respectively, by Southern blot analysis of human x Chinese hamster somatic cell hybrid panels. Recently, the corresponding genes in the mouse have been mapped to chromosomes 4 and 6 in regions that are conserved on human chromosomes 1 and 12.
Somat Cell Mol Genet 1991 Sep
PMID:Tumor necrosis factor receptor genes, TNFR1 and TNFR2, on human chromosomes 12 and 1. 166 15

The relationship between the induction of tumor necrosis factor (TNF) (as an indicator of inflammatory reaction) in tumor tissues and its antitumor effect was investigated in tumor-bearing mice by using nine biologic response modifiers (BRMs) and by exogenous/endogenous TNF therapy following a previously reported protocol. Close correlation between the induction of TNF-rich inflammation in tumor tissues and the antitumor effect of BRM were observed. The results of this study suggest that the conditions necessary for exerting antitumor effects of biologic response modifiers may be the induction of TNF (50 to 200 U/g) at the tumor lesions at an early stage after BRM administration and maintenance of the detectable amount of TNF (approximately 10 U/g) for more than 6 hours. Tumor necrosis factor should also be induced in the liver and spleen so that its activity can be maintained in the tumor lesions.
Mol Biother 1991 Dec
PMID:Intratumoral tumor necrosis factor induction in tumor-bearing mice by exogenous/endogenous tumor necrosis factor therapy as compared with systemic administration of various biologic response modifiers. 176 74

Tumor necrosis factor-alpha (TNF-alpha) is an important inflammatory mediator produced by activated monocytes and macrophages. We have previously shown that porcine alveolar macrophages (PAM) mediate bystander cytotoxicity through hydrogen peroxide production following activation with immobilized IgG immune complex (IIC) (J. Immunol. 1983; 131:1438-1442). In this report, we have investigated whether IIC induces TNF-alpha secretion by PAM. Isolated PAM from Minnesota miniature swine were cultured for 18 h with and without recombinant human interferon-gamma (rhIFN-gamma). Cultured PAM were then incubated with IIC or IgG immune complex in suspension (SIC). The supernatants generated were assessed for cytotoxic activity using a TNF-alpha-sensitive WEHI-164 cell line. Anti-recombinant human TNF-alpha (rhTNF-alpha) monoclonal antibody neutralized the observed cytotoxicity of IIC-activated PAM supernatant completely, indicating that this cytotoxicity is mediated by TNF-alpha. IIC induced TNF-alpha secretion by PAM after 3 h of incubation, reaching a plateau from 6 to 12 h and decreasing thereafter. TNF-alpha release was enhanced by pretreatment of PAM with rhIFN-gamma. SIC did not induce significant levels of TNF-alpha secretion by PAM; however, SIC with cytochalasin B-pretreated PAM induced equivalent levels of TNF-alpha secretion as IIC-activated PAM. We conclude that IIC or SIC with cytochalasin B pretreatment, both of which prevent internalization of IgG immune complex-bound Fc receptor (FcR), provide a signal for PAM to generate TNF-alpha through FcR modulation. This suggests that in vivo, deposited (immobilized) IgG immune complexes-bound FcR may be a stimulus for activation of PAM to generate TNF-alpha rather than circulating (mobilized) immune complexes, which may contribute to the pathogenesis of diffuse interstitial fibrosis of the lung, especially in idiopathic pulmonary fibrosis.
Am J Respir Cell Mol Biol 1991 Sep
PMID:Immobilized IgG immune complex induces secretion of tumor necrosis factor-alpha by porcine alveolar macrophages. 183 80

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)
Am J Respir Cell Mol Biol 1991 Aug
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.
Am J Respir Cell Mol Biol 1991 Sep
PMID:Tumor necrosis factor-induced protein phosphorylation in human neutrophils. 191 Aug 14


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