LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways
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...
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The Korean Physiological Society and The Korean Society of Pharmacology
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422967/ |
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pubmed-44229672015-05-07 LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways Lee, Seung Jin Seo, Kyo Won Kim, Chi Dae Original Article 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. The Korean Physiological Society and The Korean Society of Pharmacology 2015-05 2015-04-30 /pmc/articles/PMC4422967/ /pubmed/25954132 http://dx.doi.org/10.4196/kjpp.2015.19.3.263 Text en Copyright © 2015 The Korean Physiological Society and The Korean Society of Pharmacology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Lee, Seung Jin Seo, Kyo Won Kim, Chi Dae |
| spellingShingle |
Lee, Seung Jin Seo, Kyo Won Kim, Chi Dae LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways |
| author_facet |
Lee, Seung Jin Seo, Kyo Won Kim, Chi Dae |
| author_sort |
Lee, Seung Jin |
| title |
LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways |
| title_short |
LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways |
| title_full |
LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways |
| title_fullStr |
LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways |
| title_full_unstemmed |
LPS Increases 5-LO Expression on Monocytes via an Activation of Akt-Sp1/NF-κB Pathways |
| title_sort |
lps increases 5-lo expression on monocytes via an activation of akt-sp1/nf-κb pathways |
| description |
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. |
| publisher |
The Korean Physiological Society and The Korean Society of Pharmacology |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422967/ |
| _version_ |
1613220410543833088 |