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, 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.
Aires
Virginie
V
UPRES Lipides and Nutrition, Université de Bourgogne, Faculté des Sciences de la vie 6, Dijon, France.
Adote
Sylvie
S
Hichami
Aziz
A
Moutairou
Kabirou
K
Boustani
Es-Saddik E
ES
Khan
Naim A
NA
D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D029747:Opuntia / Q000737:chemistry*; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
D005419:Flavonoids; D007376:Interleukin-2; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D012333:RNA, Messenger; D020032:Tyrphostins; C406122:tyrphostin A9; D019284:Thapsigargin; D002118:Calcium