title: Up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 by transforming growth factor-beta1 during differentiation of human monocytes into macrophages.
abstract: Expression of acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) increases during differentiation of human monocytes into macrophages. To further elucidate the mechanism for ACAT-1 regulation in macrophages, we examined the effects of five cytokines including transforming growth factor-beta1 (TGF- beta1) on ACAT-1 expression in cultured human monocyte-macrophages. Immunoblot analyses showed that TGF-beta1 increased ACAT-1 protein expression by two- to threefold when added during differentiation of human monocytes into macrophages. ACAT activity increased in parallel by 1.8-fold. Northern blot analyses revealed that among the three ACAT-1 mRNA transcripts detected (2.8-, 3.6-, and 4.3-kb), the 2.8- and 3.6-kb transcripts were selectively increased by TGF-beta1. When TGF-beta1 was added after differentiation, ACAT-1 expression was not altered. Since TGF-beta1 is expressed in human atherosclerotic lesions, the current results suggest that ACAT-1 expression in monocytes infiltrating from the circulation to vascular walls may be enhanced by pre-existing TGF-beta1.
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hori
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Harumi
authors.initials: H
authors.lastname: Tamagawa
authors.forename: Maki
authors.initials: M
authors.lastname: Satoh
authors.forename: Kohichiro
authors.initials: K
authors.lastname: Furukawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Hakamata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Seikoh
authors.initials: S
authors.lastname: Horiuchi
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology; D009000:Monocytes / Q000166:cytology* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D002785:Sterol O-Acyltransferase