C K Wong1, J P Zhang, C W Lam, C Y Ho, N M Hjelm. 1. Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
Abstract
BACKGROUND: It has been shown that the inhibition of eosinophilic apoptosis is an important mechanism for the development of blood and tissue eosinophilia in allergic diseases. Considerable attention has recently been focused on the role played by different intracellular kinase cascades in the control of apoptosis. In the present study, we investigated the effect of sodium salicylate (NaSal), a nonsteroidal anti-inflammatory drug, on mitogen-activated protein kinases (MAPK) and apoptosis of human eosinophils. METHODS: Human blood eosinophils were purified from buffy coat. NaSal-induced apoptosis of eosinophils was assessed by morphological changes and Annexin-V binding assay. Changes of MAPK activity upon treatment with NaSal were measured by kinase activity assay and Western blot. RESULTS: NaSal could induce apoptosis of human blood eosinophils in a dose- and time-dependent manner. It could also activate c-Jun N-terminal kinase (JNK) and p38 MAPK but not extracellular signal-regulated protein kinase (ERK) activity within 1 h. Pretreatment of eosinophils with p38 MAPK and JNK anti-sense (AS) phosphorothioate oligodeoxynucleotides (ODN) or specific p38 MAPK inhibitor SB 203580 did not have any significant effect on NaSal-induced apoptosis. However, ERK AS ODNs could trigger the apoptosis of normal eosinophils. CONCLUSION: There is no direct relationship between the activation of JNK and p38 MAPK pathways and NaSal-induced apoptosis in human peripheral blood eosinophils. Copyright 2000 S. Karger AG, Basel
BACKGROUND: It has been shown that the inhibition of eosinophilic apoptosis is an important mechanism for the development of blood and tissue eosinophilia in allergic diseases. Considerable attention has recently been focused on the role played by different intracellular kinase cascades in the control of apoptosis. In the present study, we investigated the effect of sodium salicylate (NaSal), a nonsteroidal anti-inflammatory drug, on mitogen-activated protein kinases (MAPK) and apoptosis of human eosinophils. METHODS:Human blood eosinophils were purified from buffy coat. NaSal-induced apoptosis of eosinophils was assessed by morphological changes and Annexin-V binding assay. Changes of MAPK activity upon treatment with NaSal were measured by kinase activity assay and Western blot. RESULTS: NaSal could induce apoptosis of human blood eosinophils in a dose- and time-dependent manner. It could also activate c-Jun N-terminal kinase (JNK) and p38MAPK but not extracellular signal-regulated protein kinase (ERK) activity within 1 h. Pretreatment of eosinophils with p38MAPK and JNK anti-sense (AS) phosphorothioateoligodeoxynucleotides (ODN) or specific p38MAPK inhibitor SB 203580 did not have any significant effect on NaSal-induced apoptosis. However, ERK AS ODNs could trigger the apoptosis of normal eosinophils. CONCLUSION: There is no direct relationship between the activation of JNK and p38MAPK pathways and NaSal-induced apoptosis in human peripheral blood eosinophils. Copyright 2000 S. Karger AG, Basel