Phosphodiesterase 2A (PDE2A) expression is Increased by Lipopolysaccharide (LPS) through p38 and c‐Jun N‐terminal Kinase (JNK) Mitogen‐activated protein kinase (MAPK) pathways in Mouse Lung Microvascular Endothelial Cells (MLMVEC)

PDE2A is stimulated by cGMP to hydrolyze cAMP, a potent anti‐inflammatory molecule. We previously found that increased PDE2A expression can exacerbate inflammation and barrier dysfunction when cGMP levels are elevated (Schmidt et al. AJP Lung 2008). TNFα increased PDE2A expression in human umbilical vein endothelial cells through p38 MAPK (Seybold et al. Blood 2005) but less is known about PDE2A regulation in MLMVEC. To determine if MAPK pathways are involved in MLMVEC PDE2A expression, we exposed MLMVEC to LPS (1 μg/ml) in vitro. Western blotting analysis revealed that LPS increased PDE2A protein expression by 15 min with a peak effect at 6 h. LPS activated p38 and JNK MAP kinase by 5 and 15 min, respectively, with translocation of phosphorylated p38 into the nucleus at 5 min post‐LPS. The LPS‐induced increase in PDE2A expression was attenuated by a specific inhibitor of p38 (SB203580, 10 μM) or JNK (SP600125, 10 μM). We conclude that LPS increases PDE2A expression in MLMVEC through the activation of p38 and JNK MAPK pathways.