Glycogen synthase kinase-3β negatively regulates group IIA phospholipase A 2 expression in human aortic smooth muscle and HepG2 hepatoma cells

Abstract

The present study shows that the IFN-γ-mediated upregulation of secretory phospholipase A 2 of group IIA (sPLA 2-IIA) in HASMC and HepG2 cells is synergistically increased after simultaneous inhibition of glycogen synthase kinase-3β (GSK-3β) by indirubin-3 ′-monoxime, 5-iodo or AR-A014418. The effect of GSK-3β inhibition was dose- and time-dependent and can be further augmented by its concomitant incubation with Clostridium difficile toxin B, an inhibitor of small Rho proteins, or H-1152, an inhibitor of Rho-associated kinase. Using AG-490 and caffeic acid phenethyl ester (CAPE), it is further demonstrated that the effect of GSK-3β inhibition on sPLA 2-IIA expression depends on Janus kinase-2 and NF-κB-signaling.