Tumour necrosis factor-alpha-induced phosphorylation and activation of cytosolic phospholipase A(2) are abrogated by an inhibitor of the p38 mitogen-activated protein kinase cascade in human neutrophils

The role of the newly identified p38 mitogen-activated protein kinase (MAP kinase) in terminally differentiated cells, such as human neutrophils, is totally unknown. In order to examine the possible role of this MAP kinase in the phosphorylation and activation of cytoplasmic phospholipase A(2) (cPLA(2)), we tested the effect of the recently synthesized inhibitor of p38 MAP kinase, SE 203580, on the phosphorylation and activation of both p38 MAP kinase and cPLA(2). We found that while tumour necrosis factor-alpha (TNF-alpha)-stimulated tyrosine phosphorylation of p38 MAP kinase is affected only slightly by SE 203580, its stimulated kinase activity is greatly reduced in human neutrophils in suspension treated with this inhibitor. Furthermore, the TNF-alpha-stimulated phosphorylation and activation of cPLA(2) are completely abolished in cells treated with SE 203580. Based on these data, it is reasonable to conclude that an SE 203580-sensitive kinase, or kinases and/or phosphatases, are involved in the phosphorylation and activation of cPLA(2) in intact human neutrophils in suspension stimulated by TNF-alpha. The possible role of the p38 MAP kinase cascade in the phosphorylation and activation of cPLA(2) is discussed.