0000000000128968
AUTHOR
Kabirou Moutairou
Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells
Immunological tolerance is one of the fundamental aspects of the immune system. The CD4(+)CD25(+) regulatory T (Treg) cells have emerged as key players in the development of tolerance to self and foreign antigens. However, little is known about the endogenous factors and mechanisms controlling their suppressive capacity on immune response. In this study, we observed that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, diminished, in a dose-dependent manner, the capacity of Treg cells to inhibit the CD4(+)CD25(-) effector T-cell proliferation. DHA not only reduced the migration of Treg cells toward chemokines but also downregulated the mRNA expression of CCR-4 and CXCR-4 in Tr…
N-3 fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring.
We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring. Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days. Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitami…
Modulation of adipokines and cytokines in gestational diabetes and macrosomia.
Abstract Context/Objective: Not much is known about the implication of adipokines and different cytokines in gestational diabetes mellitus (GDM) and macrosomia. The purpose of this study was to assess the profile of these hormones and cytokines in macrosomic babies, born to gestational diabetic women. Design/Subjects: A total of 59 women (age, 19–42 yr) suffering from GDM with their macrosomic babies (4.35 ± 0.06 kg) and 60 healthy age-matched pregnant women and their newborns (3.22 ± 0.08 kg) were selected. Methods: Serum adipokines (adiponectin and leptin) were quantified using an obesity-related multiple ELISA microarray kit. The concentrations of serum cytokines were determined by ELISA…
Peroxisome proliferator-activated receptor alpha deficiency impairs regulatory T cell functions: Possible application in the inhibition of melanoma tumor growth in mice.
International audience; Regulatory T (Treg) cells are important to induce and maintain immunological self-tolerance. Although the progress accomplished in understanding the functional mechanism of Treg cells, intracellular molecules that control the mechanisms of their suppressive capacity are still on investigation. The present study showed that peroxisome proliferator-activated receptor-alpha deficiency impaired the suppressive activity of Treg cells on CD4(+)CD25(-) and CD8(+) T cell proliferation. In Treg cells, PPARα gene deletion also induced a decrease of migratory abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8 and CXCR-4) and p27(KIP1) mRNA. Treg ce…
Modulations physiologiques et immunologiques au cours du diabète gestationnel et de la macrosomie : implication d’une programmation in utero et nouveau concept de « mémoire métabolique »
Le diabete gestationnel est un important facteur de risque pour l’obesite fœtale et neonatale, la macrosomie. Cette revue vise a faire le point sur l’etat des connaissances actuelles sur les plans metabolique et immunologique, en insistant sur l’implication du nouveau concept de la « memoire metabolique » creee au cours du diabete gestationnel, dans la survenue des maladies metaboliques chez l’enfant lorsqu’il atteint l’âge adulte. De nombreuses etudes ont montre que les anomalies du metabolisme des hydrates de carbone et des lipides, observees chez les bebes macrosomes nes de meres diabetiques, sont dues a l’hyperglycemie maternelle qui induit l’hyperinsulinemie fœtale. Nous avons developp…
Docosahexaenoic acid and other fatty acids induce a decrease in pHiin Jurkat T-cells
Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery. Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells. To assess the role of calcium in the DHA-induced acidification, we conducted experiments in Ca2+-free (0% Ca2+) and Ca2+-containing (100% Ca2+) buffer. We observed that there was no difference in the degree of DHA-induced transient ac…
Peroxisome Proliferator-Activated Receptor Deficiency Increases the Risk of Maternal Abortion and Neonatal Mortality in Murine Pregnancy with or without Diabetes Mellitus: Modulation of T Cell Differentiation
We assessed the implication of peroxisome proliferator-activated receptor (PPAR) alpha deficiency in pregnancy outcome and neonatal survival and in the modulation of T cell differentiation in murine diabetic pregnancy and their offspring. Pregnant wild-type (WT) and PPAR alpha-null mice of C57BL/6J genetic background were rendered diabetic by five low doses of streptozotocin. We observed that, in the absence of diabetes, PPAR alpha deficiency resulted in an increase in abortion rate, i.e. 0% in WT mice vs. 20% in PPAR alpha-null mice [odds ratio (OR) = 14.33; P = 0.013]. Under diabetic conditions, the abortion rate was enhanced, i.e. 8.3% in WT mice vs. 50% in PPAR alpha-null mice (OR = 4.2…
n-3 Fatty Acids Modulate T-Cell Calcium Signaling in Obese Macrosomic Rats
Objective: We investigated the effects of a diet containing EPAX-7010, rich in PUFAs such as eicosapentaenoic acid [20:5(n-3)] and docosahexaenoic acid [22:6(n-3)], i.e., a PUFA/EPAX regimen, on T-cell activation in diabetic pregnant rats and their obese pups. Research Methods and Procedures: Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin on Day 5 of gestation. T-cell blastogenesis was assayed by using 3H-thymidine, whereas intracellular free calcium concentrations ([Ca2+]i) were measured by using Fura-2 in diabetic pregnant rats and their obese offspring. Results: Concavalin-A-stimulated T-cell proliferation was decreased in both pregnant dia…
Modulation of intracellular calcium concentrations and T cell activation by prickly pear polyphenols.
Opuntia ficus indica (prickly pear) polyphenolic compounds (OFPC) triggered an increase in [Ca2+]i in human Jurkat T-cell lines. Furthermore, OFPC-induced rise in [Ca2+]i was significantly curtailed in calcium-free buffer (0% Ca2+) as compared to that in 100% Ca2+ medium. Preincubation of cells with tyrphostin A9, an inhibitor of Ca2+ release-activated Ca2+ (CRAC) channels, significantly diminished the OFPC-induced sustained response on the increases in [Ca2+]i. Lanthanum and nifedipine, the respective inhibitors of voltage-dependent and L-type calcium channels, failed to curtail significantly the OFPC-induced calcium response. As OFPC still stimulated increases in [Ca2+]i in 0% Ca2+ medium…
Antioxidant status and circulating lipids are altered in human gestational diabetes and macrosomia.
Fetuses from mothers with gestational diabetes are at increased risk of developing neonatal macrosomia and oxidative stress. We investigated the modulation of antioxidant status and circulating lipids in gestational diabetic mothers and their macrosomic babies and in healthy age-matched pregnant women and their newborns. The serum antioxidant status was assessed by employing anti-radical resistance kit (KRL; Kirial International SA, Couternon, France) and determining levels of vitamin A, C, and E and the activity of superoxide dismutase (SOD). Circulating serum lipids were quantified, and lipid peroxidation was measured as the concentrations of serum thiobarbituric acid-reactive substances …