Implication of three isoforms of PLA(2) in human T-cell proliferation.
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.
Tessier
Christian
C
UPRES Lipides and Nutrition, Université de Bourgogne, Faculté des Sciences de la Vie, 6 Boulevard Gabriel, 21000 Dijon, France.
Hichami
Aziz
A
Khan
Naim Akhtar
NA
D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014316:Tritium
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D007527:Isoenzymes; D012333:RNA, Messenger; C081565:arachidonyltrifluoromethane; D014316:Tritium; D016718:Arachidonic Acid; D015759:Ionomycin; D010741:Phospholipases A; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium