title: Cilostazol Attenuates 4-hydroxynonenal-enhanced CD36 Expression on Murine Macrophages via Inhibition of NADPH Oxidase-derived Reactive Oxygen Species Production.
abstract: Although anti-atherogenic effects of cilostazol have been suggested, its effects on the expression of SR in macrophages are unclear. This study investigated the role of cilostazol on CD36 expression of murine macrophages enhanced by HNE, a byproduct of lipid peroxidation. The stimulation of macrophages with HNE led to an increased expression of CD36, which was significantly attenuated by NAC, an antioxidant. Moreover, the increased production of ROS by HNE was completely abolished by NADPH oxidase inhibitors, DPI and apocynin, as well as by the 5-LO inhibitor, MK886, but not by inhibitors for other oxidases. This suggested that NADPH-oxidase and 5-LO were major sources of ROS induced by HNE. In addition, HNE-enhanced expression of CD36 was reduced by these inhibitors, which indicated a role for NADPH oxidase and 5-LO on CD36 expression. In our present study, cilostazol was a significant inhibitor of ROS production, as well as CD36 expression induced by HNE. An increase in NADPH oxidase activity by HNE was significantly attenuated by cilostazol, however cilostazol had no effect on HNE-enhanced 5-LO activity. Together, these results suggest that cilostazol attenuates HNE-enhanced CD36 expression on murine macrophages thorough inhibition of NADPH oxidase-derived ROS generation.
authors.affiliation: Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 626-770, MRC for Ischemic Tissue Regeneration and Medical Research Institute, Pusan National University, Busan 602-739, Korea.
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Yun
authors.forename: Hye Mi
authors.initials: HM
authors.lastname: Park
authors.forename: Kyo Won
authors.initials: KW
authors.lastname: Seo
authors.forename: Chae Eun
authors.initials: CE
authors.lastname: Kim
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Yoon
authors.forename: Chi Dae
authors.initials: CD
authors.lastname: Kim