ANTISENSE OLIGONUCLEOTIDES TO HUMAN LIPOCORTIN-1 INHIBIT GLUCOCORTICOID-INDUCED INHIBITION OF A549 CELL-GROWTH AND EICOSANOID RELEASE

Glucocorticoids actively inhibit the growth of A549 cells by suppressi ng the release of factors such as prostaglandin E(2) (PGE(2)) necessar y for their proliferation. This effect if largely mediated through ind uction of the protein lipocortin-1. We now show that transient transfe ction of A549 cells with an antisense DNA oligonucleotide targeted to a region coding the unique N-terminal portion of human lipocortin-1 bl ocks the induction of lipocortin-1 protein following glucocorticoid tr eatment and completely reverses glucocorticoid-induced suppression of cell proliferation and PGE(2) release. A scrambled oligonucleotide was without effect. Continued culture of A549 cells in the presence of th is oligonucleotide results in a sustained increase in cell proliferati on and PGE(2) release. This study reinforces the importance of lipocor tin-1 as a negative modulator of cell growth and eicosanoid generation in this system.