title: Inhibition of VCAM-1 expression on mouse vascular smooth muscle cells by lobastin via downregulation of p38, ERK 1/2 and NF-κB signaling pathways.
abstract: Atherosclerosis is a chronic inflammatory disease, the progression of which is associated with the increased expression of cell adhesion molecules on vascular smooth muscle cells (VSMCs). Lobastin is a new pseudodepsidone isolated from Stereocaulon alpinum, Antarctic lichen, which is known to have antioxidant and antibacterial activities. However, the nature of the biological effects of lobastin still remains unclear. In the present study, we examine the effect of lobastin on the expression of vascular cell adhesion molecules (VCAM-1) induced by TNF-α in the cultured mouse VSMC cell line, MOVAS-1. Pretreatment of VSMCs for 2 h with lobastin (0.1-10 μg/ml) concentration-dependently inhibited TNF-α-induced protein expression of VCAM-1. Lobastin also inhibited TNF-α-induced production of intracellular reactive oxygen species (ROS). Lobastin abrogated TNF-α-induced phosphorylation of p38 and ERK 1/2, but not JNK, and also inhibited TNF-α-induced NK-κB activation. In addition, lobastin suppressed TNF-α-induced IκB kinase activation, subsequent degradation of IκBα and nuclear translocation of p65 NF-κB. Our results indicate that lobastin downregulates the TNF-α-mediated induction of VCAM-1 in VSMC by inhibiting the p38, ERK 1/2 and NF-κB signaling pathways and intracellular ROS generation. Thus, lobastin may be an important regulator of inflammation in the atherosclerotic lesion and a novel therapeutic drug for the treatment of atherosclerosis.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon City, Gyeonggi-do, 440-746, South Korea.
authors.forename: Kyoungran
authors.initials: K
authors.lastname: Lee
authors.affiliation: Polar BioCenter, Korea Polar Research Institute, KORDI, Incheon, Republic of Korea.
authors.forename: Joung-Han
authors.initials: JH
authors.lastname: Yim
authors.affiliation: Polar BioCenter, Korea Polar Research Institute, KORDI, Incheon, Republic of Korea.
authors.forename: Hong-Kum
authors.initials: HK
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon City, Gyeonggi-do, 440-746, South Korea. snpyo@skku.edu.
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D053630:Depsides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008011:Lichens; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D053630:Depsides; D007783:Lactones; D016328:NF-kappa B; D010936:Plant Extracts; D019010:Vascular Cell Adhesion Molecule-1; C000875:depsidone; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Atherosclerosis; Lobastin; MAPK; NF-κB; Vascular cell adhesion molecule-1