Induction of cyclooxygenase-2 (COX-2) by lipopolysaccharide (LPS) in adrenocortical Y1 cells involves activation of p38-MAPK and NFkappaB pathways

MERCAU, MARIA ELISA; ASTORT, FRANCISCO; MARTINEZ CALEJMAN, CAMILA; ARIAS, PABLO; CYMERYNG, CORA BEATRIZ

Los Cocos, Cordoba

Simposio; Spring symposium on Signal Transduction; 2010

Previous studies from our laboratory demonstrate 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 results show that LPS increases the activity of an NFkB reporter plasmid (KB-LUC) and that inhibition of this pathway blocked the stimulatory effect of LPS on COX-2 expression levels. In agreement, overexpression of p65 activates KB-LUC and upregulates COX-2 expression. In addition, LPS induces activation of p38 MAPK pathway and inhibition of this pathway blocked both KB-LUC activation and COX-2 induction by LPS. Based on these results we hypothesize that induction of COX-2 by LPS involves the activation of both NFkB and p38 MAPK signalling pathways and that activation of p38 MAPK might lead to NFkB translocation to the nucleus.