Modulation of intracellular calcium concentrations and T cell activation by prickly pear polyphenols

Mol Cell Biochem. 2004 May;260(1-2):103-10. doi: 10.1023/b:mcbi.0000026061.57326.28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Calcium / pharmacology
  • 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
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Thapsigargin / pharmacology
  • Tyrphostins / pharmacology

Substances

  • Flavonoids
  • Interleukin-2
  • Phenols
  • Plant Extracts
  • Polyphenols
  • RNA, Messenger
  • Tyrphostins
  • tyrphostin A9
  • Thapsigargin
  • Calcium