Catalase induced expression of inflammatory mediators via activation of NF-κB, PI3K/AKT, p70S6K, and JNKs in BV2 microglia

Catalase induces COX-2 or iNOS expression in some type of cells, but the mechanism remains unclear. Here we investigated the effect of catalase on COX-2 and iNOS expression in BV2 microglia and the inductive mechanism associated. Exposure of catalase to BV2 microglia induced expression of COX-2 and iNOS that was related with transcriptional up-regulation. Importantly, catalase-induced COX-2 and iNOS expression needed activations of NF-kappaB, PI3K/AKT, and JNKs, which were important for the transcriptional up-regulation of COX-2 and iNOS. Notably, rapamycin inhibition of p70S6K led to down-regulation of COX-2 and iNOS protein expression, but not steady-state mRNA expression and transcription, induced by catalase, suggesting that p70S6K is involved in increased COX-2 and iNOS mRNA translation by catalase. Interestingly, there was PI3K-dependent activation of AKT, p70S6K, JNKs, and NF-kappaB in response to catalase. These data collectively suggest catalase-induced COX-2 and iNOS expression in BV2 microglia is, in part at least, mediated through activation of multiple signaling proteins. (C) 2004 Elsevier Inc. All rights reserved.