I L - 1β에 의해 활성화 된 혈관내피 세포들에서 f e n o f i b r a t e에 의한 IL-6, IL-8, 그리고 V C A M - 1의 분비 및 발현 억제에 대한 효과
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Background : Atherosclerosis is an inflammatory disorder. Peroxisome proliferator-activated receptor (PPAR)-alpha, a member of nuclear receptor family of transcription factors, regulates the inflammatory processes of atherosclerosis. The present study investigated whether fenofibrate, a ligand of PPAR-alpha, can inhibit secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1, and expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin and activation of nuclear factor (NF)-kappaB in IL-1ⓒ￢ activated human umbilical vein endothelial cells (HUVEC). Methods : Monolayers of HUVEC were preincubated with fenofibrate at concentrations ranging 10 to 100µmol/L. Thereafter, HUVEC were activated by IL-1ⓒ￢ for 6 hours. The secretion of IL-6, IL-8, and MCP-1 and the expression of ICAM-1, VCAM-1, and E-selectin were measured by ELISA and flow cytometry. The activation of NF-kappaB was determined by electrophoretic mobility shift assay (EMSA). Results : fenofibrate (100µmol/L) strongly inhibited IL-1(mediated secretion of IL-6, IL-8 and expression of VCAM-1 on HUVEC. Also, EMSA showed that fenofibrate could reduce the activity of NF-kappaB in IL-1ⓒ￢-activated HUVEC. Conclusions : These results suggest that fenofibrate, a PPAR activator may reduce the inflammatory process of atherosclerosis by lowering of inflammatory mediators. Korean Journal of Stroke 2000;2(2): 196~201
Abstract
Background : Atherosclerosis is an inflammatory disorder. Peroxisome proliferator-activated receptor (PPAR)-alpha, a member of nuclear receptor family of transcription factors, regulates the inflammatory processes of atherosclerosis. The present study investigated whether fenofibrate, a ligand of PPAR-alpha, can inhibit secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1, and expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin and activation of nuclear factor (NF)-kappaB in IL-1ⓒ￢ activated human umbilical vein endothelial cells (HUVEC). Methods : Monolayers of HUVEC were preincubated with fenofibrate at concentrations ranging 10 to 100µmol/L. Thereafter, HUVEC were activated by IL-1ⓒ￢ for 6 hours. The secretion of IL-6, IL-8, and MCP-1 and the expression of ICAM-1, VCAM-1, and E-selectin were measured by ELISA and flow cytometry. The activation of NF-kappaB was determined by electrophoretic mobility shift assay (EMSA). Results : fenofibrate (100µmol/L) strongly inhibited IL-1(mediated secretion of IL-6, IL-8 and expression of VCAM-1 on HUVEC. Also, EMSA showed that fenofibrate could reduce the activity of NF-kappaB in IL-1ⓒ￢-activated HUVEC. Conclusions : These results suggest that fenofibrate, a PPAR activator may reduce the inflammatory process of atherosclerosis by lowering of inflammatory mediators. Korean Journal of Stroke 2000;2(2): 196~201