Up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 by transforming growth factor-β1 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-β1 (TGF-β1) on ACAT-1 expression in cultured human monocyte–macrophages. Immunoblot analyses showed that TGF-β1 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-β1. When TGF-β1 was added after differentiation, ACAT-1 expression was not altered. Since TGF-β1 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-β1.