Marked induction of sterol 27-hydroxylase activity and mRNA levels during differentiation of human cultured monocytes into macrophages.
Sterol 27-hydroxylase has been suggested to be involved in an alternative pathway for the elimination of cholesterol from macrophages and early atherosclerotic lesions. We have previously shown that human lung macrophages as well as monocyte-derived macrophages have a relatively high activity of sterol 27-hydroxylase (CYP27). This enzyme converts intracellular cholesterol into 27-hydroxycholesterol and cholestenoic acid that flux from cultured cells into the medium. It is shown here that human monocytes have very low CYP27 activity and CYP27 mRNA levels. During differentiation into macrophages, both CYP27 activity and CYP27 mRNA levels increase markedly after 4 days of culture in serum-free medium. Addition of macrophage-colony stimulating factor had no significant effect on the induction and addition of fetal calf serum had an inhibitory effect. Cholesterol synthesis was found to be a critical factor for the production of 27-oxygenated products by the macrophages cultured in serum-free medium. The increased capacity of the differentiated cells to eliminate intracellular cholesterol is of interest and supports the contention that CYP27 is an antiatherogenic factor.
Hansson
Magnus
M
Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, SE-141 86, Stockholm, Sweden.
Ellis
Ewa
E
Hunt
Mary C
MC
Schmitz
Gerd
G
Babiker
Amir
A
D002454:Cell Differentiation; D002478:Cells, Cultured; D053493:Cholestanetriol 26-Monooxygenase; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D016895:Culture Media, Serum-Free; D006801:Humans; D006888:Hydroxycholesterols / Q000032:analysis / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D019821:Simvastatin / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D013997:Time Factors
D016895:Culture Media, Serum-Free; D006888:Hydroxycholesterols; D012333:RNA, Messenger; C029435:3-hydroxy-5-cholestenoic acid; C076996:27-hydroxycholesterol; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol; D019821:Simvastatin; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase