title: TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, and MRC for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Medicine, and MRC for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, School of Medicine, and MRC for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
authors.forename: Kyo Won
authors.initials: KW
authors.lastname: Seo
authors.affiliation: Department of Pharmacology, School of Medicine, and MRC for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
authors.forename: Jin Ung
authors.initials: JU
authors.lastname: Bae
authors.affiliation: Department of Pharmacology, School of Medicine, and MRC for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
authors.forename: So Youn
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Pharmacology, School of Medicine, and MRC for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea.
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D016177:Macrophage-1 Antigen / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016177:Macrophage-1 Antigen; D051197:Toll-Like Receptor 4; D001094:Arachidonate 5-Lipoxygenase