TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium
| Autor: | Chi Dae Kim, Jin Ung Bae, Kyo Won Seo, Eun Kyoung Choi, So Youn Park, Seung Jin Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Endothelium
Physiology Science Macrophage-1 Antigen Biology Cardiovascular Physiology Monocytes Cell Line Mice Immune Physiology Molecular Cell Biology Cell Adhesion Human Umbilical Vein Endothelial Cells medicine Animals Humans Cell adhesion Molecular Biology Aorta Foam cell Mice Knockout Arachidonate 5-Lipoxygenase Multidisciplinary Cell adhesion molecule Cell Surface Molecules Soluble cell adhesion molecules Biology and Life Sciences Cell Biology Adhesion Cell biology Toll-Like Receptor 4 medicine.anatomical_structure Gene Expression Regulation Cell culture Macrophage-1 antigen Medicine Endothelium Vascular Research Article Signal Transduction |
| Zdroj: | PLoS ONE, Vol 9, Iss 8, p e104588 (2014) PLoS ONE PLOS ONE(9): 8 |
| ISSN: | 1932-6203 |
| Popis: | Toll-like receptor 4 (TLR4) is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA), a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO) inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT) mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis. |
| Databáze: | OpenAIRE |
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