5-Lipoxygenase plays a pivotal role in endothelial adhesion of monocytes via an increased expression of Mac-1
| Autor: | Kyo Won Seo, Seung Jin Lee, Yun Hak Kim, Sae-Ock Oh, So Youn Park, Eun Kyoung Choi, Jin Ung Bae, Chi Dae Kim |
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| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Endothelium Physiology Sp1 Transcription Factor Receptors Leukotriene B4 Macrophage-1 Antigen Monocytes chemistry.chemical_compound Mice Physiology (medical) Cell Line Tumor medicine Cell Adhesion Macrophage Animals Humans Foam cell Arachidonate 5-Lipoxygenase biology NF-kappa B Adhesion Cell biology Mice Inbred C57BL Toll-Like Receptor 4 medicine.anatomical_structure chemistry Macrophage-1 antigen Arachidonate 5-lipoxygenase biology.protein TLR4 Endothelium Vascular Cardiology and Cardiovascular Medicine |
| Zdroj: | Cardiovascular research. 99(4) |
| ISSN: | 1755-3245 |
| Popis: | Aims 5-Lipoxygenase (5-LO) is known to participate in the pathogenesis of atherosclerosis; however, the underlying mechanisms are unclear. Thus, this study investigated the molecular mechanisms responsible for 5-LO expression in monocytes as well as the role of 5-LO in monocyte adhesion to the vascular endothelium, which is a key early event in macrophage foam cell formation. Methods and results An en face immunohistochemistry of endothelial surfaces revealed a marked increase in monocyte adhesion to the aortic endothelium in wild-type (WT) mice treated with lipopolysaccharide (LPS), which was significantly attenuated in 5-LO(−/−) mice. Likewise, the adhesion capacity of primary monocytes isolated from LPS-treated WT mice was higher than those of monocytes from 5-LO(−/−) mice. In in vitro study, LPS increased monocyte adhesion to endothelial cells with an enhanced Mac-1 expression. These were attenuated by a 5-LO inhibitor, MK886, as well as by molecular depletion of 5-LO in monocytes. Furthermore, LPS-induced Mac-1 expression on monocytes was significantly inhibited by pre-treatment with U-75302, a BLT1-receptor antagonist, suggesting a pivotal role of 5-LO-derived leukotrienes. In promoter activity analysis and chromatin immunoprecipitation assays to identify transcription factors involved in 5-LO expression, both NF-κB and Sp1 played central roles to increase 5-LO expression in LPS-treated monocytes. Conclusion 5-LO expression in monocytes is modulated via NF-κB and Sp1 signalling pathways, and 5-LO plays a pivotal role in LPS-mediated monocyte adhesion to the vascular endothelium through an increased expression of Mac-1 on monocytes. |
| Databáze: | OpenAIRE |
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