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

Abstract

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-κB, 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-κB 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.

Abbreviations AT, 3-amino-1,2,4-triazole; ERKs, extracellular-regulated protein kinases; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; iNOS, inducible nitric oxide synthase; IκB, inhibitory kappa B; JNKs, c-Jun N-terminal kinases; NF-IL6, nuclear factor-interleukin 6; NF-κB, nuclear factor-kappa B; NO, nitric oxide; PGs, prostaglandins; PI3K, phosphatidylinositol 3 kinase; ROS, reactive oxygen species

Keywords Catalase; Microglia; COX-2; iNOS; JNK; NF-κB; PI3K/AKT/p70S6K