Tumour Necrosis Factor-α and Endotoxin Induce Less Prostaglandin E2 Production from Hypothalami of Rats Fed Coconut Oil than from Hypothalami of Rats Fed Maize Oil

1990 ◽  
Vol 79 (6) ◽  
pp. 657-662 ◽  
Author(s):  
David C. Bibby ◽  
Robert F. Grimble
Keyword(s):  
Prostaglandin E2 ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Coconut Oil ◽  
Leukotriene C4 ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
C4 Production ◽  
Necrosis Factor ◽  
Maize Oil

1. The primary aim of the study was to determine whether the stimulatory effect of tumour necrosis factor-α and endotoxin on hypothalamic prostaglandin E2 production was influenced by dietary fats containing different amounts of linoleic acid. Rats received diets containing 20% (w/w) maize oil or 19% (w/w) coconut oil plus 1% (w/w) maize oil for 8 weeks. 2. A subsidiary part of the study examined the effect of tumour necrosis factor-α on the ability of the calcium ionophore A23187 to stimulate prostaglandin E2 and leukotriene C4 production by hypothalami from chow-fed rats. 3. While tumour necrosis factor-α enhanced prostaglandin E2 production in response to A23187, neither agent had an effect on leukotriene C4 production. 4. Hypothalami from rats fed maize oil exhibited increased prostaglandin E2 production in response to both pyrogens. This did not occur with hypothalami from rats fed coconut oil. 5. Coconut oil might exert its modulatory effect by bringing about a reduction in membrane phospholipid arachidonic acid content.

scholarly journals Dietary fat modifies some metabolic actions of human recombinant tumour necrosis factor α in rats

1990 ◽  
Vol 63 (3) ◽  
pp. 653-668 ◽  
Author(s):  
D. C. Bibby ◽  
R. F. Grimble
Keyword(s):  
Tumour Necrosis Factor ◽  
Rectal Temperature ◽  
Tumour Necrosis ◽  
Coconut Oil ◽  
Liver Protein ◽  
Tumour Necrosis Factor Α ◽  
Zn Content ◽  
Factor Α ◽  
Necrosis Factor ◽  
Maize Oil

To examine how fat might influence the metabolic effects of tumour necrosis factor α (TNFα), human recombinant TNFα was given intravenously to rats that had been fed for 12 weeks on diets containing (g/kg) 200 maize oil or 190 coconut oil+10 maize oil. Rectal temperature and tissue composition measurements were made 8 and 24 h after injection. Ambient temperatures of 20° and 25° were employed to accentuate rectal temperature changes. Doses of 30 and 300 μg TNFα/kg body-weight were given, and brought about depression of serum zinc and albumin and elevation of copper. Muscle protein content was decreased and liver protein and Zn content enhanced by TNFα. Serum Zn and liver Zn content were negatively correlated 8 h after injections. Hypothermia developed within 1 h of injection. All responses except the rise in serum Cu and gain in liver Zn were more intense at the higher than at the lower dose of TNFα. Hypothermia was exacerbated by an environmental temperature of 20°. The coconut-oil diet blunted the hypothermia and likewise the changes in serum albumin and Cu content 8 h after injections and in muscle and liver protein after 24 h. Changes in eicosanoid metabolism may be involved in the modulatory effects of the coconut-oil-enriched diet.

Influence of butter and of corn, coconut and fish oils on the effects of recombinant human tumour necrosis factor-α in rats

1993 ◽  
Vol 84 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Hilda M. Mulrooney ◽  
Robert F. Grimble
Keyword(s):  
Protein Synthesis ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Coconut Oil ◽  
Complement C3 ◽  
Tumour Necrosis Factor Α ◽  
Zinc Concentrations ◽  
Factor Α ◽  
Lung And Kidney ◽  
Necrosis Factor

1. Tumour necrosis factor-α is produced in response to inflammatory stimuli. Fish oil can suppress the production and actions of cytokines. Little information is available on the effects of other fats on cytokine biology. We compared the effects of fats, with a wide range of fatty acid characteristics, on the effects of tumour necrosis factor-α on protein and zinc metabolism in rats. 2. Weanling rats were fed for 8 weeks on diets containing 10% fat in the form of corn, fish or coconut oils or butter before an intraperitoneal injection of recombinant human tumour necrosis factor-α was given. Measurements were made 24 h after the injection. 3. In rats fed corn oil, food intake was reduced by 62% and rates of protein synthesis were increased by 86, 32 and 39% in the liver, lung and kidney, respectively. Zinc concentrations increased by 23% in the liver but decreased by 10% in the kidney. Plasma caeruloplasmin and complement C3 levels increased by 25% and 28%, respectively, and plasma albumin level decreased by 24%. 4. Fish oil prevented the increase in hepatic protein synthesis and changed the response of protein synthesis in lung and kidney to a decrease. Changes in hepatic and renal zinc concentrations were prevented. The response of the plasma caeruloplasmin level was unaltered but those of the plasma complement C3 and albumin concentrations were prevented. 5. Coconut oil and butter, although similarly low in linoleic acid, differed in their modulatory effects. With the exception of the rise in the plasma complement C3 concentration, all responses were prevented or greatly inhibited in rats fed butter. In rats fed coconut oil the increase in liver protein synthesis was reduced but that in the lung and kidney was unaffected. Changes in hepatic zinc concentration were unaffected but those in renal zinc concentration were prevented. 6. Fish and coconut oils and butter reduced the intensity of anorexia caused by tumour necrosis factor-α. The extent to which fats rich in (n-3) polyunsaturates or poor in linoleic acid modulate the metabolic response to tumour necrosis factor-α depends upon additional fatty acid characteristics.

Induction of Enhanced Responsiveness of Human Articular Chondrocytes to Extracellular ATP by Tumour Necrosis Factor-α

1993 ◽  
Vol 85 (5) ◽  
pp. 569-575 ◽  
Author(s):  
Weng S. Leong ◽  
R. Graham ◽  
G. Russell ◽  
Alison M. Caswell
Keyword(s):  
Articular Cartilage ◽  
Prostaglandin E2 ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Articular Chondrocytes ◽  
Extracellular Atp ◽  
Human Articular Chondrocytes ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

1. We have observed previously that extracellular ATP acting at P2-purinoceptors promotes the production of prostaglandin E2 by human articular chondrocytes, and that this response is enhanced synergistically by interleukin-1β. Since other cytokines that influence the metabolism of articular cartilage may have a similar effect, we have investigated whether tumour necrosis factor-α also modulates the stimulation of the production of prostaglandin E2 in these cells by ATP. 2. Tumour necrosis factor-α enhanced the response of cultured human articular chrondrocytes to a maximally stimulating concentration of ATP (100 μmol/l). This effect was present when the cells were co-incubated with tumour necrosis factor-α and ATP for 4 h, was augmented when the cells were also preincubated with the cytokine for 24 h, and remained constant or declined on extending the preincubation period to 72 h. The enhancement of responsiveness to ATP by tumour necrosis factor-α was dose-dependent, and the minimum effective concentration (6 pmol/l) did not consistently increase prostaglandin E2 production when the cytokine was tested alone. The presence of tumour necrosis factor-α during the incubation with ATP was required for maximum enhancement of the response. Tumour necrosis factor-α did not alter the minimum concentration of ATP that stimulated production of prostaglandin E2. 3. Cytokines such as interleukin-1 and tumour necrosis factor-α are involved in the pathogenesis of some forms of arthritis, and these data provide additional evidence that their actions in articular cartilage may be modulated by other agents which originate from chondrocytes. Moreover, although both these cytokines enhance responsiveness of human articular chondrocytes to extracellular ATP, differences in their effects were observed which suggest that they may act independently.

Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

2003 ◽  
Vol 70 ◽  
pp. 39-52 ◽  
Author(s):  
Roy A. Black ◽  
John R. Doedens ◽  
Rajeev Mahimkar ◽  
Richard Johnson ◽  
Lin Guo ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Recent Work ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transforming Growth Factor ◽  
Intrinsic Activity ◽  
Converting Enzyme ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

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