Lipopolysaccharide induction of REDD1 is mediated by two distinct CREB-dependent mechanisms in macrophages

REDD1 is induced by various cellular stresses; however, its expression in response to lipopolysaccharide (LPS) has not been clearly elucidated in immune cells. LPS stimulated CREB-dependent and NF-κB-independent REDD1 expression in macrophages. Early increases in CREB phosphorylation and REDD1 expression at 8 h following LPS treatment were blocked by inhibition of p38MAPK and mitogen- and stress-activated protein kinase 1 (MSK1), but not PKA. However, delayed CREB-mediated REDD1 expression at 16 h was suppressed by inhibition of cyclooxygenase-2 (COX-2) and PKA. It indicates that LPS induces REDD1 expression by two distinct CREB-mediated mechanisms, the early p38MAPK/MSK1 and the delayed COX-2/PGE2/PKA pathways.