Implication of three isoforms of PLA(2) in human T-cell proliferation

FEBS Lett. 2002 Jun 5;520(1-3):111-6. doi: 10.1016/s0014-5793(02)02779-5.

Abstract

We observed that human (Jurkat) T-cells constitutively expressed the mRNA, encoding for the four isoforms of phospholipase A(2) (PLA(2)), i.e. two secretory (type IB and type V), and two cytosolic (type IV, Ca(2+)-dependent and type VI, Ca(2+)-independent). In order to assess whether these PLA(2) isoforms are active, we labeled Jurkat T-cells with [(3)H]arachidonic acid ([(3)H]AA) and determined its release into the extracellular medium in the presence of phorbol 12-myristate 13-acetate (PMA) and ionomycin. The three PLA(2) isoforms seem functional as aristolochic acid and bromoenol lactone (BEL), the respective inhibitors of type IB/type V and type VI PLA(2)s, significantly inhibited the release of free [(3)H]AA. On the other hand, arachidonyl trifluoromethyl ketone (AACOCF(3)), an inhibitor of type IV PLA(2), failed to curtail significantly the release of free [(3)H]AA into the extracellular medium. We assessed the implication of these PLA(2) isoforms in transcription of the interleukin-2 (IL-2) gene, involved in T-cell proliferation. Hence, aristolochic acid and BEL, but not AACOCF(3), significantly inhibited the PMA and ionomycin-induced induction of mRNA of IL-2. Similarly, aristolochic acid and BEL, but not AACOCF(3), significantly inhibited the PMA and ionomycin-induced secretion of IL-2 in the culture supernatants. Together these results suggest that human Jurkat T-cells possess two secretory and two cytosolic PLA(2) isoforms and only three of them (type IB, type V and type VI) are implicated in T-cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / metabolism
  • Arachidonic Acids / pharmacology
  • Calcium / metabolism
  • Cell Division / drug effects
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Interleukin-2 / genetics
  • Ionomycin / pharmacology
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Jurkat Cells / cytology
  • Jurkat Cells / drug effects
  • Jurkat Cells / metabolism*
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A / genetics
  • Phospholipases A / metabolism*
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tritium

Substances

  • Arachidonic Acids
  • Enzyme Inhibitors
  • Interleukin-2
  • Isoenzymes
  • RNA, Messenger
  • arachidonyltrifluoromethane
  • Tritium
  • Arachidonic Acid
  • Ionomycin
  • Phospholipases A
  • Tetradecanoylphorbol Acetate
  • Calcium