Sodium salicylate-induced apoptosis of human peripheral blood eosinophils is independent of the activation of c-jun N-terminal kinase and p38 mitogen-activated protein kinase

Background: It has been shown that the inhibition of eosinophilic apoptosis is an important mechanism for the development of blood and tissue eosinoph ilia in allergic diseases. Considerable attention has recently been focused on the role played by different intracellular kinase cascades in the contr ol of apoptosis, In the present study, we investigated the effect of sodium salicylate (NaSaI), a nonsteroidal anti-inflammatory drug, on mitogen-acti vated protein kinases (MAPK) and apoptosis of human eosinophils. Methods: H uman blood eosinophils were purified from buffy coat. NaSaI-induced apoptos is of eosinophils was assessed by morphological changes and Annexin-V bindi ng assay. Changes of MAPK activity upon treatment with NaSaI were measured by kinase activity assay and Western blot. Results: NaSaI could induce apop tosis of human blood eosinophils in a dose- and time-dependent manner. It c ould also activate c-Jun N-terminal kinase (JNK) and p38 MAPK but not extra cellular signal-regulated protein kinase (ERK) activity within 1 h. Pretrea tment of eosinophils with p38 MAPK and JNK anti-sense (AS) phosphorothioate oligodeoxynucleotides (ODN) or specific p38 MAPK inhibitor SE 203580 did n ot have any significant effect on NaSaI-induced apoptosis. However, ERK AS ODNs could trigger the apoptosis of normal eosinophils. Conclusion: There i s no direct relationship between the activation of JNK and p38 MAPK pathway s and NaSaI-induced apoptosis in human peripheral blood eosinophils. Copyri ght (C) 2000 S. Karger AG, Basel.