11 Beta-hydroxysteroid dehydrogenase type 1 is induced in human monocytes upon differentiation to macrophages.
11beta-hydroxysteroid dehydrogenases (11beta-HSD) perform prereceptor metabolism of glucocorticoids through interconversion of the active glucocorticoid, cortisol, with inactive cortisone. Although the immunosuppressive and anti-inflammatory activities of glucocorticoids are well documented, the expression of 11beta-HSD enzymes in immune cells is not well understood. Here we demonstrate that 11beta-HSD1, which converts cortisone to cortisol, is expressed only upon differentiation of human monocytes to macrophages. 11beta-HSD1 expression is concomitant with the emergence of peroxisome proliferator activating receptor gamma, which was used as a surrogate marker of monocyte differentiation. The type 2 enzyme, 11beta-HSD2, which converts cortisol to cortisone, was not detectable in either monocytes or cultured macrophages. Incubation of monocytes with IL-4 or IL-13 induced 11beta-HSD1 activity by up to 10-fold. IFN-gamma, a known functional antagonist of IL-4 and IL-13, suppressed the induction of 11beta-HSD1 by these cytokines. THP-1 cells, a human macrophage-like cell line, expressed 11beta-HSD1 and low levels of 11beta-HSD2. The expression of 11beta-HSD1 in these cells is up-regulated 4-fold by LPS. In summary, we have shown strong expression of 11beta-HSD1 in cultured human macrophages and THP-1 cells. The presence of the enzyme in these cells suggests that it may play a role in regulating the immune function of these cells.
Thieringer
R
R
Department of Atherosclerosis and Endocrinology, Merck Research Laboratories, Rahway, NJ 07065, USA. rolf_thieringer@merck.com
Le Grand
C B
CB
Carbin
L
L
Cai
T Q
TQ
Wong
B
B
Wright
S D
SD
Hermanowski-Vosatka
A
A
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D018793:Interleukin-13; D008070:Lipopolysaccharides; D015847:Interleukin-4; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate