Catalase induced expression of inflammatory mediators via activation of NF-kappaB, 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.
Jang
Byeong-Churl
BC
Chronic Disease Research Center and Institute for Medical Science, Keimyung University School of Medicine, #194 DongSan-Dong, Jung-Gu, Daegu 700-712, South Korea. jangbc12@kmu.ac.kr
Paik
Ji-Hye
JH
Kim
Sang-Pyo
SP
Shin
Dong-Hoon
DH
Song
Dae-Kyu
DK
Park
Jong-Gu
JG
Suh
Min-Ho
MH
Park
Jong-Wook
JW
Suh
Seong-Il
SI
D000818:Animals; D002374:Catalase / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2; D004789:Enzyme Activation; D018836:Inflammation Mediators / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D015533:Transcriptional Activation
D002374:Catalase; D051546:Cyclooxygenase 2; D018836:Inflammation Mediators; D048031:JNK Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D011451:Prostaglandin-Endoperoxide Synthases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D020123:Sirolimus; C496317:Nos2 protein, mouse