トヨダ　ナガオキ   TOYODA NAGAOKI   豊田　長興    所属   関西医科大学  内科学第二講座    職種   診療教授
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	The regulation of EN-RAGE (S100A12) gene expression in human THP-1 macrophages.
掲載誌名	正式名：Atherosclerosis 略　 称：Atherosclerosis ISSNコード：00219150
巻・号・頁	171(2),pp.211-218
著者・共著者	Hasegawa T, Kosaki A, Kimura T, Matsubara H, Mori Y, Okigaki M, Masaki H, Toyoda N, Inoue-Shibata M, Kimura Y, Nishikawa M, Iwasaka T
発行年月	2003/12
概要	EN-RAGE is a ligand for the receptor for advanced glycation end products (RAGE) and may be involved in the development of diabetic macro- and micro-angiopathy. This study is designed to investigate the regulation of EN-RAGE gene expression in human macrophages. The amounts of EN-RAGE mRNA were measured in cultured human THP-1 macrophages after treatment with various stimuli known to modulate atherosclerosis. First, interleukin-6 (IL-6), a proinflammatory cytokine, increased the level of EN-RAGE mRNA by approximately 2-fold in a time- and a dose-dependent fashion. EN-RAGE protein was detected in the cultured medium and increased significantly by the addition of IL-6. The induction was abolished by pretreatment with the JAK kinase inhibitor and cycloheximide, but not with the MEK kinase inhibitor. Second, pioglitazone (PIO), a thiazolidinedione, decreased the level of EN-RAGE mRNA by approximately 25% of the basal in a time- and a dose-dependent fashion. Pioglitazone also inhibited the induction of EN-RAGE mRNA by IL-6. These results indicate the production of EN-RAGE is induced by IL-6 through de novo protein synthesis via the JAK-STAT kinase pathway and inhibited by the activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) in human macrophages.
文献番号	14644389