Opposing effects of sodium salicylate and haematopoietic cytokines IL-3, IL-5 and GM-CSF on mitogen-activated protein kinases and apoptosis of EoL-1 cells.
Haematopoietic cytokines such as IL-3, IL-5 and GM-CSF not only activate eosinophils but also prolong their life span by inhibiting their apoptotic cell death. We have studied the effects of IL-3, IL-5 and GM-CSF on apoptosis and mitogen-activated protein kinases (MAPKs) in a human eosinophilic leukaemic cell line (EoL-1). Results demonstrated that all three cytokines could trigger the receptor-mediated activation of extracellular signal-regulated kinase (ERK) within one hour but not p38 MAPK activity in EoL-1 cells. In contrast, sodium salicylate (NaSal), a nonsteroidal anti-inflammatory drug (NSAID), could activate p38 MAPK but not ERK within one hour. Both cytokines and specific p38 MAPK inhibitor SB 203580 could partly block the NaSal-induced apoptosis in EoL-1 cells. A specific MAPK/ERK kinase (MEK) inhibitor, PD 098059, could induce apoptosis and eliminate the protective effect of IL-3, IL-5 and GM-CSF against NaSal-induced apoptosis in EoL-1 cells. Taken together, cytokines IL-3, IL-5 and GM-CSF could prolong EoL-1 cells survival through the transient activation of ERK. On the other hand, activation of p38 MAPK in EoL-1 cells by NaSal could lead to apoptosis. Activation of p38 MAPK and the resulting induction of apoptosis in EoL-1 cells may be important to explain the anti-inflammatory action of NSAID in allergic inflammation.
Wong
C K
CK
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT.
Zhang
J P
JP
Lam
C W
CW
Ho
C Y
CY
Hjelm
N M
NM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D017681:Hypereosinophilic Syndrome; D007093:Imidazoles / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012980:Sodium Salicylate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D007377:Interleukin-3; D015848:Interleukin-5; D011725:Pyridines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D012980:Sodium Salicylate