INDUCTION OF CYCLOOXYGENASE-2 (COX-2) BY LIPOPOLYSACCHARIDE (LPS) IN ADRENOCORTICAL Y1 CELLS INVOLVES ACTIVATION OF P38-MAPK AND NFkB PATHWAYS

MARÍA E. MERCAU; FRANCISCO ASTORT; CAMILA MARTINEZ CALEJMAN; PABLO ARIAS; CORA B. CYMERYNG

Simposio; The First South American Spring Symposium in Signal Transduction and Molecular Medicine; 2010

Previous studies from our laboratory demonstrated that LPS increases the production of glucocorticoids in a murine adrenocortical cell line (Y1). We have also shown that LPS increases the expression of COX-2, and hence the production of prostaglandins, potential modulators of adrenal steroidogenesis. In addition COX inhibitors have been shown to block the LPS-dependent increase in progesterone production. Present experiments were designed to analyze the signaling pathways involved in the regulation of COX-2 expression by LPS in Y1 cells. Our findings in Y1 cells are: LPS induces COX-2 expression in a time-dependent manner Both NFκB and p38 MAPK pathways are activated by LPS Selective inhibitors of either of these pathways produce a partial blockage of LPS-dependent COX-2 induction and in the increase of progesterone levels Activation of the NFkB pathway leads to an increase of COX-2 expression levels Selective blockage of the p38 MAPK pathway does not alter LPS-dependent activation of the NFkB pathway LPS-dependent COX-2 induction might involve the independent activation of NFkB and p38 MAPK pathways, leading to prostanoid synthesis, which potentially modulate steroid production in Y1 cells.