Up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 by transforming growth factor-beta1 during differentiation of human monocytes into macrophages.
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.
Hori
Masaharu
M
Department of Medical Biochemistry, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Miyazaki
Akira
A
Tamagawa
Harumi
H
Satoh
Maki
M
Furukawa
Kohichiro
K
Hakamata
Hideki
H
Sasaki
Yutaka
Y
Horiuchi
Seikoh
S
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*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D002785:Sterol O-Acyltransferase