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Query: HUMANGGP:017444 (TNF)
 61,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acquired renal cysts derive from terminally differentiated tubular epithelium in adults as a consequence of increased epithelial cell proliferation, fluid accumulation and extracellular matrix remodelling. To understand better how human epithelial cysts may be initiated and progressively expand, cells from primary cultures of normal human adult renal cortex were dispersed in polymerized type I collagen. The transparent matrix permitted repeated observation by light microscopy of cyst formation from individual renal cells. The cyst cells reacted strongly with distal nephron histochemical markers (cytokeratin antibodies AE1/AE3, epithelial membrane antigen, and Arachis hypogaea lectin) but inconsistently or not at all to markers of proximal tubules (Tetragonolobus purpureas lectin and Phaseolus vulgaris erthroagglutinin lectin). The number of spherical, fluid-filled epithelial cysts that developed in a standardized microscope field quantified cyst initiation. Cyst progression was determined from the increase in the diameter (surface area) of cysts and represents a hyperplastic event. EGF or TGF alpha, were required in serum-free defined medium to cause cysts to develop from individual epithelial cells dispersed in the matrix; insulin was required as a co-factor. The EC50 for EGF was approximately 0.1 ng/ml, and for insulin 1 microgram/ml. Early cultures of normal cortex formed cysts more efficiently when dispersed in collagen matrix than cells passaged several times before suspension in the gel. Agonists of adenylate cyclase (PGE1, AVP, VIP, PTH, forskolin, cholera toxin), methylisobutylxanthine, and 8-Br-cAMP, though incapable of causing cyst formation alone in defined medium, enhanced cyst initiation and progression in the presence of EGF and insulin. Angiotensin II, TNF alpha, beta-estradiol, and pertussis toxin had no effect in the absence or presence of EGF and insulin. Pertussis toxin inhibited cyst initiation and expansion caused by EGF and forskolin but potentiated cyst initiation and expansion caused by EGF and PGE1. Cyst formation and expansion were inhibited by TGF beta 1 and 2-chloroadenosine. Polarized monolayers of human renal cortical cells grown on permeable membranes were used to independently quantify the effects of agonists on the net secretion of solute and water from the basolateral to the apical surface of the cells. PGE1, forskolin, and 8-Br-cAMP stimulated net fluid secretion that was sustained for several days; EGF enhanced forskolin-stimulated fluid secretion. We conclude that the formation and expansion of in vitro cysts derived from solitary human cortex cells depends on the coordinated interplay between cellular proliferation and fluid secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro formation and expansion of cysts derived from human renal cortex epithelial cells. 131 21

We investigated the effects of tobacco smoke exposure on the production of tumor necrosis factor alpha (TNF alpha) by alveolar macrophages (AM) in mice (C57BL/6). The results obtained are as follows: (1) In vivo tobacco smoke exposure caused a significant decrease in the production of TNF alpha by AM with the stimulation of lipopolysaccharide (LPS; control group: 19.32 +/- 5.52 U/ml, smoked group: 4.28 +/- 0.98 U/ml; p less than 0.05). (2) In vitro exposure of AM to tobacco smoke extracts (water-soluble extracts) also caused a decrease in the production of TNF alpha up to 93% of control with stimulation of LPS (p less than 0.05) without any decrease in cellular viability. We concluded that the production of TNF alpha by AM was impaired by smoking via direct action of the factors present in tobacco smoke.
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PMID:Inhibition of mouse alveolar macrophage production of tumor necrosis factor alpha by acute in vivo and in vitro exposure to tobacco smoke. 162 Sep 85

Platelet-activating factor (PAF) is a glycerophospholipid known for its unusual potent vasoactive and proinflammatory activities. The present study examined whether PAF might serve as a priming factor in endotoxin-induced tumor necrosis factor-alpha (TNF alpha) synthesis, cardiovascular shock, and lung injury in anesthetized rats. Intravenous infusion of PAF (1 pmol/kg/min for 60 minutes, n = 5) alone or endotoxin (0.1 micrograms/kg i.v. bolus, n = 5) failed to alter blood pressure, serum TNF alpha and thromboxane B2, platelet and leukocyte count, and hematocrit, nor was lung histology, myeloperoxidase activity, and water content changed. In contrast, the combined administration of PAF and endotoxin markedly elevated serum TNF alpha (1,359 +/- 362 pg/ml, n = 5, p less than 0.01) and thromboxane B2 (43 +/- 5 pg/100 microliters, n = 8, p less than 0.01) along with hypotension, hemoconcentration, leukopenia, and thrombocytopenia. Most notably, the combined regimen caused neutrophil aggregation, adhesion, and accumulation into the lung parenchyma along with platelet-fibrin deposits in postcapillary venules, pulmonary edema, and increased lung myeloperoxidase activity. The role of PAF in this process was confirmed by 1) the prevention of the priming effect by pretreatment with the PAF antagonist BN 50739 (n = 5), and 2) the failure of lyso-PAF, the cardinal nonactive PAF-metabolite, to prime for endotoxin-induced production of TNF alpha (n = 4). These data suggest that PAF could serve as a key mediator in priming for endotoxin-induced tissue injury, especially the typical pulmonary pathophysiology of adult respiratory distress syndrome, a severe pathological outcome of septic shock, burns, and multiple organ injury.
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PMID:Priming by platelet-activating factor of endotoxin-induced lung injury and cardiovascular shock. 164 75

The biological stains, methylene blue and its metabolite azure B, were evaluated as anti-tumor and anti-inflammatory agents. Azur B, administered in drinking water to tumor-bearing mice, inhibited the growth of transplanted tumors and the growth of primary tumors induced by methylcholanthrene. Inhibition of growth of primary tumors was observed only in female mice. Azure B also reduced the wet weight of carrageenin-induced granulomas in rats. Azure B, given intravenously to BCG-sensitized mice 15 minutes prior to challenge with lipopolysaccharide, decreased TNF production (to 10% of control values) and prevented death from endotoxic shock. Methylene blue decreased TNF production (to 50% of control values) but did not protect the animals from endotoxic shock. Our results suggest that some of the effects previously ascribed to methylene blue are probably mediated via its metabolite, i.e. azure B. Low toxicity and easy administration of the dyes explain their use in clinical settings.
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PMID:Anti-tumoral and anti-inflammatory effects of biological stains. 181 Jan 51

We sought evidence of cytokine presence and interleukin-1 beta (IL-1 beta) bioactivity in 104 aerobic culture negative cyst fluids (CFs) from 13 kidneys of 13 patients with symptomatic normal to end-stage autosomal dominant polycystic kidney disease (ADPKD). ELISAs were used to detect IL-1 beta, interleukin-2 (IL-2), tumor necrosis factor alpha (TNF alpha) and stromelysin. Prostaglandin E2 (PGE2) was detected by radioimmunoassay. IL-1 beta was present in 65 of 94 (less than 20 to 419 pg/ml, TNF alpha in 54 of 75 (less than 10 to 73 pg/ml), stromelysin in 18 of 23 (less than 1.0 to 56 ng/ml), IL-2 in 7 of 23 (0.1 to 1.3 ng/ml) and PGE2 in 9 of 10 fluids (0.03 to 0.49 ng/ml). Of 51 fluids with immunoreactive IL-1 beta, 36 were mitogenic for thymocytes. IL-1 beta concentrations correlated directly with those of IL-2; IL-1 beta presence was associated with higher stimulation indices, higher mean concentrations of TNF alpha, IL-2, stromelysin, and PGE2, and with positive endotoxin assays, suggesting activation of the cytokine cascade in vivo. Cytokine, stromelysin and PGE2 concentrations did not correlate with sodium or non-sodium solute concentrations, nor with CF blood, osmolality, or endotoxin activity, indicating that differences in concentrations among fluids could not be explained by differences in water content. These data identify cytokines as candidate contributors to the morbidity and pathogenesis of ADPKD.
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PMID:Cytokines in fluids from polycystic kidneys. 205 29

Tracheal insufflation of tumor necrosis factor (TNF; 5 micrograms or 1.2 x 10(5) U) markedly enhanced the survival of adult rats exposed to 100% O2: 12 of 17 rats (71%) survived for greater than 11 days, whereas 30 of 30 control (Hanks' balanced salt solution) insufflated rats (100%) died within 3 days of O2 exposure. Insufflation of gamma-interferon (5 micrograms) or intraperitoneal injection of up to 40 micrograms TNF did not afford any protection. At 55 h after O2 exposure, TNF-insufflated rats showed less pulmonary edema, as determined by the extravascular lung water content-to-bloodless lung dry weigh ratio and less alveolar capillary leak as determined by the protein content in the bronchoalveolar lavage fluid, than control insufflated rats similarly exposed. This protection against O2 toxicity by TNF insufflation was associated with increased lung superoxide dismutase, catalase, and glutathione peroxidase activities. The enhancement of lung antioxidant enzyme activities was noted at 55 h of O2 exposure, when control animals began to die of O2 toxicity. This temporal relationship suggests that TNF-induced increase in antioxidant enzyme activities contributes, at least in part, to the observed protection.
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PMID:Tracheal insufflation of tumor necrosis factor protects rats against oxygen toxicity. 234 45

Previous studies have shown that the activation of murine macrophages to a fully tumoricidal state requires that specific environmental signals be delivered to the macrophage in a step-wise manner: a "priming" signal first renders the macrophage stimulated, but not cytolytic. The addition of a second or "trigger" signal to the primed macrophage results in tumoricidal activity. One potent priming signal has been identified as IFN-gamma and one often used trigger signal for endotoxin-responsive (Lpsn) macrophages is LPS. In contrast to LPS-responsive macrophage, rIFN-gamma-primed C3H/HeJ (Lpsd) macrophages fail to become cytolytic in response to protein-free, phenol-water-extracted LPS preparations, but become tumoricidal when exposed in vitro to protein-rich butanol-extracted LPS or purified lipid A-associated proteins. Further characterization of the activation requirements of the C3H/HeJ macrophages revealed that for optimal elaboration of TNF in vitro, two signals were also required: rIFN-gamma and a second signal that contained LAP. C3H/HeJ macrophages macrophages primed with rIFN-gamma failed to produce TNF in response to any concentration of protein-free phenol-water extracted LPS, even when supernatants were concentrated before assaying for functional activity in a standard TNF L929 fibroblast assay. Although exposure of rIFN-gamma-primed C3H/HeJ macrophages to LAP resulted in a fully tumoricidal state equivalent to that exhibited by C3H/OuJ macrophages, the levels of TNF produced remained discrepant. Under identical conditions, C3H/OuJ macrophages produced approximately fivefold more TNF (11,776 U/ml) than C3H/HeJ macrophages (2,399 U/ml). This suggests that although C3H/HeJ macrophages can respond functionally in a "normal" manner given the correct signals, they remain quantitatively deficient in the production of certain proteins. In this system, the elaboration of TNF and macrophage-mediated tumor cell lysis were shown to be dissociable events. The tumor target used in these studies (P815) was shown to be resistant to as much as 40,000 U/ml of purified rTNF. In addition, C3H/OuJ macrophage cultures exposed to LPS only (which resulted in the production of high levels of TNF), failed to lyse these targets. Lastly, anti-mouse TNF antibody added to macrophage cultures had no effect on the induction of tumor cell lysis.
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PMID:Production of tumor necrosis factor by rIFN-gamma-primed C3H/HeJ (Lpsd) macrophages requires the presence of lipid A-associated proteins. 314 60

As a result of the incubation of Escherichia coli in normal human serum, a finite fraction of LPS is released from the bacterial membrane. Approximately half of the LPS released by the action of serum (S-LPS) exists in association with serum proteins in a lower m.w. form than that manifest in phenol-water extracted LPS preparations. The two major LPS-serum protein complexes have apparent Mr of 68 and 32 kDa. The LPS subunit heterogeneity of S-LPS, however, does not appear to differ significantly from LPS retained on the bacteria after serum treatment, or from LPS derived by lysis of whole cells. The biologic activities of S-LPS and phenol-water extracted LPS examined in these studies, differed significantly. In contrast to phenol-water extracted LPS, S-LPS was 1) reduced in lethal toxicity for sensitized mice; 2) reduced in Limulus reactivity; 3) a more potent murine splenocyte mitogen; 4) reduced in the capacity to elicit extracellular, but not membrane-associated IL-1; and 5) reduced in the ability to mediate TNF production. These data suggest that humoral "detoxification" of LPS may involve, in part, the formation of LPS-serum protein complexes with reduced capacities to elicit extracellular cytokine production, whereas the immunomodulatory effects of LPS appear to be enhanced.
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PMID:The physical-chemical characterization and biologic activity of serum released lipopolysaccharides. 326 29

The effect of bacterial lipopolysaccharide (LPS), muramyl dipeptide (MDP) and their combination on the production of tumour necrosis factor by spleen cells in vitro and on tumour regression in vivo has been studied. TNF activity was detected in spleen cell supernatants and serum of mice treated with drugs, using L929 cells as targets. The combination of LPS and MDP was more effective in TNF production than each of the drugs used alone in vitro and in vivo. The injection of LPS and MDP to A/Sn mice with subcutaneous nodes of sarcoma SA-I resulted in total tumour necrosis. The treatment of mice with these drugs in water solutions was more effective, however, more toxic than the administration of LPS-treated splenocytes in MDP solution.
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PMID:[Activation of the production of the tumor-necrosis factor by the combined action of lipopolysaccharide and muramyl dipeptide in vitro and in vivo]. 331 36

A comparison has been made of the cachectic effects produced by the transplantable murine adenocarcinoma of the mouse colon (MAC16) with tumour necrosis factor-alpha (cachectin). Tumour necrosis factor-alpha (TNF-alpha) produced a dose-related weight reduction that was accompanied by a decrease in both food and water intake. The degree of weight loss was directly proportional to the decreased food and water intake. In contrast weight loss produced by the MAC16 tumour occurred without a reduction in fluid or nutrient intake. Both the MAC16 tumour and TNF-alpha produced hypoglycaemia and a reduction in the circulatory level of free fatty acids (FFA), but had opposite effects on the level of plasma triglycerides with the MAC16 tumour-induced cachexia causing a decrease and TNF-alpha producing an increase. The MAC16 tumour elaborated a lipolytic factor which caused an immediate release of FFA from adipose tissue. In contrast TNF-alpha had no effect on mobilization of adipose triglycerides over a short time period. Both TNF-alpha and extracts from the MAC16 tumour caused an enhanced release of amino acids from mouse diaphragm, which was suppressible with indomethacin and heat labile. No TNF was detected in the MAC16 tumour or in the serum of tumour-bearing animals. Both tumour and non-tumour-bearing animals responded with a similar elevation of their serum TNF levels 90 min after a single injection of endotoxin. It is concluded that weight loss produced by TNF-alpha arises from an anorexic effect and that this differs from the complex metabolic changes associated with cancer cachexia.
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PMID:Comparison of weight loss induced by recombinant tumour necrosis factor with that produced by a cachexia-inducing tumour. 339 Mar 73


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