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D Duval

Publications and source records attributed to D Duval.

At least 73 records · Page 4Linked to original sources
PubMed1986

Pharmacological modulation of prostaglandin production by phagocytic cells of the thymic reticulum in relation to immunoregulation.

We cultured phagocytic cells derived from the thymic reticulum in order to study the regulation of prostaglandin (PG) production by antiinflammatory or immunostimulating agents. The kinetics of PGE2, 6-keto-PGF1 alpha and PGF2 alpha production were measured by specific radioimmunoassays of the supernatants harvested from cells treated with dexamethasone, a steroidal antiinflammatory drug and by two non steroidal inhibitors (indomethacin and sulindac) or by various immunostimulating agents, one of them, RU 41740 is currently being used in humans. Our results revealed that each of these drugs exerts a differential effect on the PG production, with a striking action on PGE2 synthesis, a lesser effect on 6-keto-PGF1 alpha production and almost no effect on PGF2 alpha synthesis. The possible mechanisms responsible for this complex regulation of PG production are discussed.

Adjuvants, Immunologic↗
PubMed1986

Effect of serum on the metabolism of exogenous arachidonic acid by phagocytic cells of the mouse thymic reticulum.

Phagocytic cells derived from the mouse thymic reticulum (P-TR) were used to study the effect of serum on the metabolism of arachidonic acid (AA). After labeling with (14C)-AA in the presence of 10% serum, we failed to detect in the culture medium the presence of significant amounts of radiolabeled prostaglandins. In contrast, when the labeling period was carried out in serum-free medium, we observed the secretion of both cyclooxygenase and lipoxygenase derivatives. In addition, the pattern of arachidonate incorporation into cell lipids was different in the two culture conditions. In the presence of serum, the great majority of the radioactivity was found associated with phospholipids, whereas in serum-free medium, almost 50% of the incorporated fatty acid was associated with triglycerides. Since serum albumin is known to play a major role in the control of fatty acid uptake, we have studied the effect of the addition of 2% BSA to cells prelabeled in the absence of serum. This treatment switches the patterns of metabolite release and lipid labeling towards those of serum-treated cells. In addition, we showed that the effects of glucocorticoids on AA release differ markedly according to the composition of the culture medium.

Animals↗
PubMed1986

Dexamethasone binding sites and steroid-dependent stimulation of glycogenesis by insulin in cultured fetal hepatocytes.

The binding of [3H]dexamethasone and the effect of insulin on [14C]glucose incorporation into glycogen were studied in cultures of fetal rat hepatocytes transplanted from 15 and 18 days of gestation, i.e. before and just at the critical stage of glucocorticoid-dependent maturation of the rat fetus. Both types of cell cultures contained approximately 50,000 specific glucocorticoid receptors per cell, with an affinity of 6 nM. Glycogenesis was hardly stimulated by insulin at the time of transplantation, especially in 15-day-old fetal hepatocytes. The stimulatory effect of insulin increased in the presence of dexamethasone (100 nM) to reach, after 40 h of treatment, 270% and 440% of the control values in 15- and 18-day-old fetal hepatocytes, respectively. A shortening of the exposure time to steroid necessary to trigger the insulin response was observed with 18-day-old cells (20 h). The half-maximal insulin-induced stimulation of glycogenesis was obtained with a lower concentration of dexamethasone in 18-day-old than in 15-day-old hepatocytes (3.2 +/- 0.32 vs. 7.9 +/- 0.29 nM, n = 5; P less than 0.001). Although high affinity dexamethasone binding sites exist in fetal rat hepatocytes before the critical stage of glucocorticoid influences, some maturation occurs between the 15th and the 18th day of gestation, which is associated with an increase in cell sensitivity to dexamethasone and in the amplitude of the steroid-induced glycogenic response to insulin.

Animals↗
PubMed1985

Synthesis of 7 alpha- and beta-carboxymethyl derivatives of cortisol, corticosterone, deoxycorticosterone and cortisone. Immunogenic properties of cortisol, corticosterone and deoxycorticosterone derivatives.

7 alpha- and 7 beta-Carboxymethylderivatives of cortisol, corticosterone and deoxycorticosterone have been synthetized. After coupling to bovine serum albumin, they were used to elicit antibodies in rabbits. Highly specific antisera were obtained which may possibly be used for a direct radioimmunoassay of these steroids in human and rodent plasma. In the case of the derivatives of cortisol and corticosterone and stereoisomery of the coupling had an effect on the affinity and the specificity of the antisera. In all immunized rabbits the antisera obtained with the 7 alpha-derivative had a higher affinity and a narrower specificity than the antiserum obtained with the 7 beta-derivative.

Antibody Affinity↗
PubMed1985

Autoradiographic study of the nuclear transfer of the antiglucocorticoid compound RU38486 in mouse tissues.

In order to investigate the mode of action of RU38486, a recently described antiglucocorticoid molecule, we have studied by autoradiography the localization of [3H]RU38486 in various glucocorticoid target tissues 30 and 60 min following in vivo injection. The results obtained in brain, liver and kidney sections clearly demonstrate that [3H]RU38486 is specifically translocated in target cell nuclei. Indeed, the nuclear labelling observed after injection of the tracer was significantly decreased after injection of [3H]RU38486 in the presence of a 100-fold excess of unlabelled RU38486. The distribution of the specific labelling of RU38486 within the central nervous system was very similar to that previously described for dexamethasone with an accumulation of radioactivity in the cell nuclei of the hypothalamic area of the nucleus arcuatus. Our results thus provide additional evidence for an action of this antiglucocorticoid molecule at the nuclear level.

Animals↗
PubMed1985

Opposite effects of a glucocorticoid and an immunostimulating agent on prostaglandin production by two different cell types.

Studies were performed to investigate the effects of several agents known to modulate wound healing on prostaglandin production by mouse embryo fibroblasts and adult thymic phagocytic cells in culture. Dexamethasone (10(-6)M) induced in both cell types a significant inhibition of the production of PGE2 and 6 keto PGF1 alpha, and a moderate inhibition of PGF2 alpha. Using an antiglucocorticoid compound, RU 38486, we were able to demonstrate that the inhibition of PG secretion represents a classical receptor-mediated effect of the steroid. In contrast, LPS and RU 41740 (5 micrograms/ml) induced a significant stimulation of PGE2 and 6-keto-PGF1 alpha secretion in the two types of cells. These results suggest that agents which modulate in different ways the process of tissue repair have opposite effects on PG production by cells involved in inflammatory and/or immunological reactions.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Prostaglandin production by phagocytic cells of the mouse thymic reticulum in culture and its modulation by indomethacin and corticosteroids.

The production of prostaglandins by phagocytic cells of the thymic reticulum in culture (P-TR) was studied by using high pressure liquid chromatography and radioimmunoassay. Radioimmunologic determinations showed that thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha (6 keto-PGF1 alpha) were the major compounds released into the culture medium, whereas prostaglandin F2 alpha (PGF2 alpha) was only a minor component. Indomethacin and dexamethasone exerted a similar pattern of differential inhibition of the secretion of prostanoids. PGE2 and 6-keto PGF1 alpha productions were markedly decreased by these anti-inflammatory drugs, whereas those of TXB2 and PGF2 alpha were not or were only slightly affected. Experiments performed with an antiglucocorticoid compound (RU 38486) showed that the steroid-induced inhibition of prostanoid secretion is a classical receptor-mediated action. These results demonstrated that phagocytic cells of the thymic reticulum, which resemble the thymic interdigitating cells, produce several types of prostaglandins. Because it has been described that P-TR regulate thymocyte proliferation in vitro via the secretion of both interleukin 1 and PGE2, these results suggest that anti-inflammatory agents may be able to modulate the thymic microenvironment and, consequently, thymocyte proliferation.

Animals↗
PubMed1984

Effect of antiglucocorticoids on dexamethasone-induced inhibition of uridine incorporation and cell lysis in isolated mouse thymocytes.

We have compared in isolated mouse thymocytes the action of progesterone, cortexolone, DXH (a 17-beta carboxamide derivative of dexamethasone) and RU 38486 (a new antiglucocorticoid molecule), on dexamethasone-induced inhibition of uridine incorporation and cell lysis, with the affinities of these drugs for glucocorticoid receptors. Our results show that progesterone, cortexolone and DXH which possess similar affinities for glucocorticoid receptors may exhibit variable, weak agonist and antagonist activities according to the parameter studied. RU 38486 was a potent competitor of dexamethasone and was able, when present in a 10-fold excess, to counteract almost completely the inhibitory action as well as the lytic action of 5 X 10(-8) M dexamethasone. This compound which exerts almost no agonist activity may therefore represent a useful tool to investigate the mode of action of antiglucocorticoids.

17-Hydroxycorticosteroids↗
PubMed1984

Role of adrenal hormones and prostaglandins in the control of mouse thymocytes lysis.

The cytolytic actions of glucocorticoids and of agents increasing cyclic AMP were studied in vitro in thymocyte suspensions isolated from adrenalectomized or hydrocortisone-treated mice. Although considered as corticoresistant cells, the thymocytes isolated from hydrocortisone-treated mice were lysed to the same extent although more slowly in vitro by dexamethasone than whole thymocyte populations (i.e. corticosensitive cells). Moreover, these two cell populations were shown to contain comparable amounts of glucocorticoid receptors and to be almost equally sensitive to the metabolic effects of glucocorticoids when measured by inhibition of RNA and DNA synthesis. Studies performed with corticosensitive cells showed that prostaglandin E2, isoproterenol and dibutyrilcyclic AMP were also able to induce cell lysis and that, isoproterenol and dexamethasone exerted additive cytolytic action in vitro. In vivo experiments showed also an additive effect of steroids and isoproterenol on thymus atrophy. In contrast, cells isolated from hydrocortisone-treated animals were not sensitive to the cytotoxic action of prostaglandin E2, isoproterenol and dibutyril cyclic AMP. This difference between the two populations was not associated with any difference in the responsiveness of adenylate cyclase as determined following isoproterenol-induced accumulation of cyclic AMP. The cytolytic action of dexamethasone but also that of prostaglandin E2 and isoproterenol, could be blocked in the presence of cycloheximide, an inhibitor of protein synthesis, thus suggesting that glucocorticoids and agents increasing cyclic AMP control the synthesis of some proteins involved in the triggering of cell lysis. Among the hypotheses proposed to explain the differences between in vitro and in vivo sensitivity of lymphoid cell to glucocorticoids, it was suggested that the drug may in vivo indirectly control the viability or the proliferation of thymocytes through the release of other mediators. We have shown that in vivo injection of hydrocortisone induces an accumulation of fatty acids in the whole thymus gland but not in the isolated thymocytes. Since exogenous fatty acids exert cytolytic actions on isolated thymocytes, we suggest that glucocorticoids may exert in vivo an indirect toxic action by promoting the release of fatty acids from adipose tissue or other sources.

Animals↗
PubMed1983

Angiotensin II does not elicit any specific prostaglandin secretion in piglet cultured endothelial cells.

PGE2 and PGF2 alpha were measured in culture media from piglet aortic endothelial cells by radioimmunological analysis. Prostacyclin secretion was evaluated by radioimmunological analysis of its stable metabolite, 6-keto-PGF1 alpha after reverse-phase high pressure liquid chromatography separation. No stimulation of either prostaglandin was detectable in culture media after treatment with angiotensin II (10(-9) to 10(-6) M) for 15 to 120 min at 37 degrees C. Under the same conditions angiotensin II (10(-7) M) elicited a 2 to 3 fold increase in PGE2 and PGF2 alpha secretion when incubated with cultured piglet aortic smooth muscle cells. In addition, we failed to detect specific angiotensin receptors at the surface of intact cultured endothelial cells. Since there was a very rapid increase in prostaglandin secretion after washing or medium changes we suggested that the effects of Angiotensin II on prostacyclin production, demonstrated in perfused organs, could be due to the mechanical stimulation elicited by the contraction of the underlying smooth muscle cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Potentiation by steroids of the beta-adrenergic agent-induced stimulation of cyclic AMP in isolated mouse thymocytes.

There is an increasing amount of evidence suggesting that glucocorticoids may modulate the responsiveness of various cell types to beta-adrenergic agents. In some systems, it has been shown, in addition, that steroids potentiate the elevation of cAMP induced by catecholamines. Little is known however of the mechanism underlying steroid action. We have studied this 'permissive action' in isolated thymocytes which have specific receptor sites for both glucocorticoids and beta-adrenergic agents. The glucocorticoid compound dexamethasone did not alter intracellular cAMP level but markedly enhanced the stimulation produced by isoproterenol. This effect was instantaneous and was still measurable at 10(-7) M dexamethasone. A similar potentiating action was observed in the presence of corticosterone but also in the presence of sex steroids. Determination of beta-receptors after cell preincubation in the presence of dexamethasone showed that rapid alterations in beta-receptors are not involved in this permissive action. Experiments done in the presence of the calcium chelator, ethyleneglycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, suggest that dexamethasone action could be related to a modification of calcium mobilization.

Animals↗
PubMed1983

Differential effects of sex steroids on prostaglandin secretion by male and female cultured piglet endothelial cells.

The effect of sex steroids, 17 beta-estradiol and testosterone, on the production of 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha and prostaglandin E2 was studied in cultures of piglet aorta endothelial cells. In cells isolated from female animals both steroids stimulated the secretion of prostaglandins. In contrast, sex steroids did not affect prostaglandin synthesis by endothelial cells taken from male animals. In addition, female endothelial cells convert testosterone into estriol, estrone and estradiol. Estradiol-induced stimulation of prostacyclin production may explain in part the beneficial role generally attributed to naturally occurring estrogens in cardiovascular diseases.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Arachidonate incorporation and prostaglandin production in cultured endothelial and smooth muscle cells from pig aorta.

In order to investigate the utilization of arachidonic acid by vascular cells, we have compared cultured endothelial and smooth muscle cells from piglet aorta, after a 24 hour incubation with [ 3H ]-arachidonic acid [( 3H ] -AA). We studied both the release of labeled cyclo-oxygenase products, and the distribution of the radioactive fatty acid among lipids as determined by thin layer chromatography. As already described by others the main prostaglandins (PG) released by endothelial cells were PGF2 alpha and 6 keto-PGF1 alpha whereas smooth muscle cells mainly produced PGE2. These differences were associated with marked modification of the radioactivity distribution among the various lipid classes. In particular, the proportion of [ 3H ] -AA incorporated into neutral lipids was much more important in smooth muscle than in endothelial cells (approximately 40% of the total incorporated radioactivity versus 8%). On the other hand, the distribution of [ 3H ] -oleic acid into cell lipids after a 24 hour incorporation was very similar in both types of cells. These results suggest the existence of precise mechanisms controlling the incorporation and the availability of the PG precursor in the various types of cells. This might in part explain the differences observed for different cell types in the PG secretion pattern.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Specific binding and pharmacological interactions of apamin, the neurotoxin from bee venom, with guinea pig colon.

This paper describes the interaction of apamin, the bee venom neurotoxin, with its receptor in the guinea pig colon. The pharmacological activity of the toxin was assayed by measuring its contracting effect on guinea pig colon preparations that had been previously relaxed by neurotensin. The IC50 value of apamin in this in vitro bioassay is 7 nM. These pharmacological data are compared to the binding properties of apamin to smooth muscle membranes prepared from guinea pig colon. The highly radiolabeled monoiododerivative of apamin binds to its colon receptor with a dissociation constant Kd* = 36 pM. The maximal binding capacity of colonic membranes is 30dfmol/mg of protein. The dissociation constant of the unmodified toxin is 23 pM. The difference between the toxin concentrations that produce half-maximal effects in the binding and pharmacological studies arises from the different experimental conditions used for the two assays.

Animals↗