Induction of 11beta-hydroxysteroid dehydrogenase type 1 but not -2 in human aortic smooth muscle cells by inflammatory stimuli.
The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes catalyze the interconversion of active glucocorticoids (GC) with their inert metabolites, thereby regulating the functional activity of GC. While 11beta-HSD type 1 (11beta-HSD1) activates GC from their 11-keto metabolites, 11beta-HSD type 2 (11beta-HSD2) inactivates GC. Here we report that both of these enzymes are expressed in human aortic smooth muscle cells (SMC), and that 11beta-HSD1 is more abundant and is differentially regulated relative to 11beta-HSD2. Stimulation of SMC with IL-1beta or TNFalpha led to a time- and dose-dependent increase of mRNA levels for 11beta-HSD1, while 11beta-HSD2 mRNA levels decreased. Parallel enzyme activity studies showed increased conversion of 3H-cortisone to 3H-cortisol but not 3H-cortisol to 3H-cortisone, demonstrating 11beta-HSD1 in SMC acts primarily as a reductase. A similar increase of 11beta-HSD1 mRNA expression was also found in human bronchial SMC upon stimulation, indicating the regulatory effect is not limited to vascular smooth muscle. Additional parallel studies revealed a similar pattern of induction for 11beta-HSD1 and monocyte chemoattractant protein-1, a well-defined proinflammatory molecule. These data suggest 11beta-HSD1 may play an important role in regulating inflammatory responses in the artery wall and lung.
Cai
T Q
TQ
Department of Lipid Biochemistry, Merck Research Laboratories, RY80W-250 126 East Lincoln Avenue, Rahway, NJ 07065, USA. tianquan_cai@merck.com
Wong
B
B
Mundt
S S
SS
Thieringer
R
R
Wright
S D
SD
Hermanowski-Vosatka
A
A
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D001011:Aorta / Q000166:cytology / Q000201:enzymology*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004790:Enzyme Induction; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D017931:DNA Primers; D018836:Inflammation Mediators; D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human