Biomedical subjects

F Homo-Delarche

Publications and source records attributed to F Homo-Delarche.

79 records · Page 5Linked to original sources

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

Thymic reticulum in mice. III. Phagocytic cells of the thymic reticulum in culture secrete both prostaglandin E2 and interleukin 1 which regulate thymocyte proliferation.

A phagocytic cell of the thymic reticulum in culture (P-TR-C) has recently been isolated whose characteristics closely resemble those of the thymic interdigitating cell despite the modifications induced by culture conditions. In the present report it is demonstrated that this cell population is able to produce both interleukin 1 (IL 1) and prostaglandin E2 (PGE2). IL 1 has no direct mitogenic effect on thymocytes but is comitogenic with concanavalin A. PGE2 has no direct effect on the secretion of IL 1 by P-TR-C, but has an effect antagonistic to IL 1, inhibiting thymocyte proliferation. P-TR-C are thus able to modulate thymocyte proliferation in vitro.

Animals↗

PubMed1983

Cytolytic effects of dexamethasone and of agents stimulating cyclic AMP content in isolated mouse thymocytes.

The cytolytic action of glucocorticoids and of agents increasing cyclic AMP were studied in corticosensitive and corticoresistant mouse thymocyte populations. Studies performed in corticosensitive cells showed that prostaglandin E2, isoproterenol and dibutyryl cyclic AMP were also able to induce cell lysis. Moreover, isoproterenol and dexamethasone exerted additive cytolytic effects. In contrast, cells isolated from hydrocortisone-treated animals were only moderately sensitive to the cytotoxic action of dexamethasone in vitro and insensitive to the action of prostaglandin E2, isoproterenol and dibutyryl cyclic AMP. Finally, we showed that 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.

Animals↗

PubMed1983

Effect of immunostimulating and anti-inflammatory agents on the biosynthesis of prostaglandins E2, F2 alpha, prostacyclin (PGI2) and thromboxane a2 (TXA2) by mouse embryo fibroblasts in tissue culture.

Experiments performed in cultures of mouse embryo fibroblasts have shown that dexamethasone (10(-6) M) significantly inhibits the production of PGE2 and PGI2 but only moderately inhibits that of PGF2 alpha. Conversely, lipopolysacharide treatment (5 micrograms/ml) markedly stimulated the secretion of PGE2 and PGI2 and only slightly that of PGF2 alpha. In these cultures, the secretion of TXA2 remained unaffected either in the presence of dexamethasone or LPS.

6-Ketoprostaglandin F1 alpha↗

PubMedDate not supplied

Effect of glucocorticoids on arachidonic acid metabolism and prostaglandin secretion by cultures of newborn rat heart cells.

We described that oxygen deprivation induced in cultures of heart muscle cells, biochemical events similar to those described in ischemic tissue: arachidonic acid liberation, loss of membrane phospholipids and increase in neutral lipids. Since glucocorticoids have been described to inhibit phospholipase activity and to exert beneficial effects during myocardial infarction, we studied in our experimental model the action of dexamethasone on the metabolism of arachidonic acid and on the synthesis of immunoreactive prostaglandins. Our results show that heart muscle cells produce prostaglandin E2 and 6-keto-prostaglandin-F1 alpha. This synthesis, inhibited by dexamethasone (70% inhibition), decreased after oxygen-deprivation (-45%). The effect of oxygen deprivation and dexamethasone (-60%) are not additive. Moreover, steroid treatment failed to counteract the loss of polyunsaturated fatty acids from the phospholipids, the increase in neutral lipids and the liberation of arachidonic acid induced by oxygen deprivation in muscle cells. These results may indicate that the cardiovascular effects of glucosteroids are not the consequence of a direct effect on heart metabolism at cellular level.

6-Ketoprostaglandin F1 alpha↗

PubMedDate not supplied

Thymic expression of the pancreatic endocrine hormones.

The thymus plays a central role in the selection of T lymphocytes that are tolerant to 'self' antigens and responsive to foreign pathogens. We and others have reported the expression of the pancreatic endocrine hormones, preproinsulin, proglucagon, prosomatostatin and propancreatic polypeptide in the human and mouse thymus. While mRNA expression is very low there is evidence for the presence of the translated product. In addition, we have investigated the cell types responsible for expression. In the thymus, hormone expression is enriched in the antigen-presenting cell population. Interestingly, while proglucagon, prosomatostatin and propancreatic polypeptide appear to be expressed in a macrophage population, preproinsulin expression was restricted to dendritic cells which are more potent antigen-presenting cells. The functional significance of the endogenous expression of insulin in the thymus has been indirectly investigated using transgenic models in which the transgene is introduced by the rat insulin promoter. The data suggest that thymic expression of the transgene is critical in the induction of T-cell tolerance to the transgene in the periphery. Taken together, the evidence suggests that the low-level pancreatic hormone expression in the thymus may be involved in central tolerance to proteins of restricted expression.

Animals↗

PubMedDate not supplied

PCR analysis of interleukin-1 receptor gene in the nonobese diabetic mouse.

Insulin-dependent diabetes mellitus (IDDM) is characterized by a progressive autoimmune destruction of pancreatic beta cells. Many data suggest that interleukin 1 (IL-1) plays a fundamental role in the pathogenesis of the disease. In the nonobese diabetic (NOD) mouse, a spontaneous model of IDDM, it was put forward that the disease is linked to a susceptibility locus, called idd5, which contains the IL-1 receptor (IL-1R) gene. The polymerase chain reaction (PCR) was used to characterize the IL-1R gene in our NOD mouse colony and in two mouse strains taken as controls. Using primers to amplify the IL-1R gene between bp-106 and +378, a 580 bp fragment was obtained from C57BL/6 DNA but not from DBA/2 and NOD DNA. However, amplification of the IL-1R gene region between bp +1 and +378 in the three strains yielded amplicons 480 bp long. The specificity of the amplification was confirmed by restriction analysis. Our results suggest, depending on the strain, the presence of one or two introns: one (480 bp) in the 5'-untranslated region and the other (100 bp) in the region coding for amino acids between 69 and 126, and an exon-intron organization of the mouse IL-1R gene different than that described in the human genome.

Amino Acid Sequence↗