Induction of cyclooxygenase-2 in macrophages by catalase: role of NF-kappaB and PI3K signaling pathways.
Induction of COX-2 by catalase in smooth muscle cells, endothelial cells, and neuronal cells has been previously reported. However, the mechanism by which catalase up-regulates COX-2 remains poorly understood. In this study, we investigated the effect of catalase on induction of COX-2 in macrophages. The addition of catalase into Raw 264.7 macrophages induced COX-2 expression that was correlated with increased COX-2 transcription and mRNA stability. Catalase also induced activation of NF-kappaB, PI3K, ERKs, p38s, or JNKs. Catalase-induced COX-2 expression was abrogated by treatment of MG-132 (a NF-kappaB inhibitor) or LY294002 (a PI3K inhibitor), but not by treatment of PD98059 (an ERK inhibitor), SB203580 (a p38 inhibitor), or SP600125 (a JNK inhibitor). Moreover, inhibition of PI3K by LY294002 caused partial decrease of catalase-induced COX-2 transcription and steady-state COX-2 transcript levels, but not COX-2 mRNA stability. Together, these results suggest that catalase induces the expression of COX-2 in Raw 264.7 macrophages, and the induction is related with activation of NF-kappaB transcription factor and PI3K signaling pathway.
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
Kim
Do-Hyun
DH
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
Kim
Sang-Pyo
SP
Song
Dae-Kyu
DK
Park
Jong-Gu
JG
Bae
Jae-Hoon
JH
Mun
Kyo-Chul
KC
Baek
Won-Ki
WK
Suh
Min-Ho
MH
Hla
Timothy
T
Suh
Seong-Il
SI
D000818:Animals; D002374:Catalase / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2; D004790:Enzyme Induction; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
D007527:Isoenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; D002374:Catalase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019869:Phosphatidylinositol 3-Kinases