Abstract
Epidermal growth factor (EGF) rapidly stimulates the release of arachidonic acid in A549 cells by a mechanism that is sensitive to pertussis toxin [1]. We show that EGF treatment of A549 cells stimulates phosphorylation of cytosolic phospholipase A 2 (cPLA 2) through a mechanism that is similarly inhibited by pertussis toxin. The level of cPLA 2 expression is, apparently, not changed during this period. Pretreatment of cells with dexamethasone (10–100 nM) for 3 hr prevents this activation of cPLA 2 by EGF, without changing the level of cPLA 2 expression. The effect of dexamethasone is reversed in the presence of the neutralizing antilipocortin Mab 1A but not by the nonneutralizing antilipocortin 1 control Mab 1B. This strongly suggests that lipocortin 1 mediates the effect of dexamethasone by inhibiting activation of cPLA 2. This concept is supported by the fact that a peptide Lc13-25 (10–200 μg/mL), derived from the N-terminus of lipocortin 1, also inhibits activation of cPLA 2 by EGF in these cells.
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