Modulation of intracellular calcium concentrations and T cell activation by prickly pear polyphenols.
Fiche publication
Date publication
mai 2004
Journal
Molecular and cellular biochemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr KAHN Naim, Dr HICHAMI Aziz, Dr AIRES Virginie
Tous les auteurs :
Aires V, Adote S, Hichami A, Moutairou K, Boustani ES, Khan NA
Lien Pubmed
Résumé
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, the role of intracellular calcium was investigated. Hence, addition of thapsigargin (TG), an inhibitor of Ca2+-ATPase of the endoplasmic reticulum (ER), during the OFPC-induced peak response exerted an additive effect, indicating that the mechanism of action of these two agents are different. Furthermore, U73122, an inhibitor of IP3 production, completely abolished increases in [Ca2+]i, induced by OFPC, suggesting that these polyphenols induce the production of IP3 that recruits calcium from ER pool. Polyphenolic compounds do act extracellularly as addition of fatty acid-free bovine serum albumin (BSA) significantly diminished the rise in [Ca2+]i evoked by the formers. OFPC also induced plasma membrane hyperpolarisation which was reversed by addition of BSA. OFPC were found to curtail the expression of IL-2 mRNA and T-cell blastogenesis. Together these results suggest that OFPC induce increases in [Ca2+]i via ER pool and opening of CRAC channels, and exert immunosuppressive effects in Jurkat T-cells.
Mots clés
Calcium, metabolism, Calcium Signaling, drug effects, Dose-Response Relationship, Drug, Flavonoids, pharmacology, Gene Expression, drug effects, Humans, Interleukin-2, genetics, Jurkat Cells, Lymphocyte Activation, drug effects, Membrane Potentials, drug effects, Opuntia, chemistry, Phenols, pharmacology, Plant Extracts, pharmacology, Polyphenols, RNA, Messenger, genetics, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, drug effects, Thapsigargin, pharmacology, Tyrphostins, pharmacology
Référence
Mol. Cell. Biochem.. 2004 May;260(1-2):103-10