LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways

• 영문명: LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Seung Jin Lee Kyo Won Seo Chi Dae Kim
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제19권 제3호, 263~268쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2015.01.01

영문 초록

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.

키워드

Akt Atherosclerosis LPS Monocytes 5-Lipoxygenase