Induction of 11β-hydroxysteroid dehydrogenase type 1 but not-2 in human aortic smooth muscle cells by inflammatory stimuli

The 11 beta -hydroxysteroid dehydrogenase (11 beta -HSD) enzymes catalyze the interconversion of active glucocorticoids (GC) with their inert metabolites, thereby regulating the functional activity of GC. While LIP-HSD type 1 (11 beta -HSD1) activates GC from their 1 l-keto metabolites, 11 beta -HSD type 2 (11 beta -HSD2) inactivates GC. Here we report that both of these enzymes are expressed in human aortic smooth muscle cells (SMC), and that 11 beta -HSD1 is more abundant and is differentially regulated relative to 11 beta -HSD2. Stimulation of SMC with IL-I beta or TNF alpha led to a time- and dose-dependent increase of mRNA levels for 11 beta -HSD1, while 11 beta -HSD2 mRNA levels decreased. Parallel enzyme activity studies showed increased conversion of H-3-cortisone to H-3-cortisol but not H-3-cortisol to H-3-cortisone, demonstrating 11 beta -HSD1 in SMC acts primarily as a reductase. A similar increase of 11 beta -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 11 beta -HSD1 and monocyte chemoattractant protein-1, a well-defined proinflammatory molecule. These data suggest 11 beta -HSD1 may play an important role in regulating inflammatory responses in the artery wall and lung. (C) 2001 Elsevier Science Ltd. All rights reserved.