The Co-Ordinate Regulation of Lipocortin 1, Cox 2 and CPLA₂ by IL-1β in A549 Cells

Abstract

In the A549 human lung adenocarcinoma cell line, generation of prostaglandin E₂ (PGE₂) is an important regulator of cell proliferation in vitro (1). Both epidermal growth factor (EGF) and the pro-inflammatory cytokine IL-1β up regulate cell proliferation by inducing PGE₂ release. The PGE₂ mediated increase in cell proliferation can be inhibited by dexamethasone. The inhibition of PGE₂ release by the dexamethasone is mediated via the induction of lipocortin 1 on the surface of A549 cells (1). Furthermore, we have shown the EGF simulated arachidonic acid release, PGE₂ release and subsequent cell proliferation can all be repressed by the addition of fragments of lipocortin-1 to the cells (2). These results imply that cell surface lipocortin 1 can regulate arachidonic acid release, and when EGF simulated cells are treated with dexamethasone the increase in cell surface lipocortin 1 is responsible for down-regulating arachidonic acid release, PGE₂ release and cell proliferation.