title: LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways.
abstract: 5-Lipoxygenase (5-LO) plays a pivotal role in the progression of atherosclerosis. Therefore, this study investigated the molecular mechanisms involved in 5-LO expression on monocytes induced by LPS. Stimulation of THP-1 monocytes with LPS (0~3 µg/ml) increased 5-LO promoter activity and 5-LO protein expression in a concentration-dependent manner. LPS-induced 5-LO expression was blocked by pharmacological inhibition of the Akt pathway, but not by inhibitors of MAPK pathways including the ERK, JNK, and p38 MAPK pathways. In line with these results, LPS increased the phosphorylation of Akt, suggesting a role for the Akt pathway in LPS-induced 5-LO expression. In a promoter activity assay conducted to identify transcription factors, both Sp1 and NF-κB were found to play central roles in 5-LO expression in LPS-treated monocytes. The LPS-enhanced activities of Sp1 and NF-κB were attenuated by an Akt inhibitor. Moreover, the LPS-enhanced phosphorylation of Akt was significantly attenuated in cells pretreated with an anti-TLR4 antibody. Taken together, 5-LO expression in LPS-stimulated monocytes is regulated at the transcriptional level via TLR4/Akt-mediated activations of Sp1 and NF-κB pathways in monocytes.
authors.affiliation: Department of Pharmacology and BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan 626-870, Korea.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan 626-870, Korea.
authors.forename: Kyo Won
authors.initials: KW
authors.lastname: Seo
authors.affiliation: Department of Pharmacology and BK21 Medical Science Education Center, School of Medicine, Pusan National University, Yangsan 626-870, Korea.
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
keywords: 5-Lipoxygenase; Akt; Atherosclerosis; LPS; Monocytes