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 eo sinophils but also prolong their life span by inhibiting their apoptotic ce ll 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 leuk aemic cell line (EoL-1). Results demonstrated that all three cytokines coul d trigger the receptor-mediated activation of extracellular signal-regulate d 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 cytokin es and specific p38 MAPK inhibitor SE 203580 could partly block the NaSal-i nduced 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 surviv al through the transient activation of ERK. On the other hand, activation o f p38 MAPK in EoL-1 cells by NaSal could lead to apoptosis. Activation of p 38 MAPK and the resulting induction of apoptosis in EoL-1 cells may be impo rtant to explain the anti-inflammatory action of NSAID in allergic inflamma tion.