| First Author | Coutinho AE | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 1 | Pages | 234-40 |
| PubMed ID | 22067318 | Mgi Jnum | J:181651 |
| Mgi Id | MGI:5312187 | Doi | 10.1210/en.2011-1398 |
| Citation | Coutinho AE, et al. (2012) 11beta-Hydroxysteroid dehydrogenase type 1, but not type 2, deficiency worsens acute inflammation and experimental arthritis in mice. Endocrinology 153(1):234-40 |
| abstractText | Glucocorticoids profoundly influence immune responses, and synthetic glucocorticoids are widely used clinically for their potent antiinflammatory effects. Endogenous glucocorticoid action is modulated by the two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). In vivo, 11beta-HSD1 catalyzes the reduction of inactive cortisone or 11-dehydrocorticosterone into active cortisol or corticosterone, respectively, thereby increasing intracellular glucocorticoid levels. 11beta-HSD2 catalyzes the reverse reaction, inactivating intracellular glucocorticoids. Both enzymes have been postulated to modulate inflammatory responses. In the K/BxN serum transfer model of arthritis, 11beta-HSD1-deficient mice showed earlier onset and slower resolution of inflammation than wild-type controls, with greater exostoses in periarticular bone and, uniquely, ganglion cysts, consistent with greater inflammation. In contrast, K/BxN serum arthritis was unaffected by 11beta-HSD2 deficiency. In a distinct model of inflammation, thioglycollate-induced sterile peritonitis, 11beta-HSD1-deficient mice had more inflammatory cells in the peritoneum, but again 11beta-HSD2-deficient mice did not differ from controls. Additionally, compared with control mice, 11beta-HSD1-deficient mice showed greater numbers of inflammatory cells in pleural lavages in carrageenan-induced pleurisy with lung pathology consistent with slower resolution. These data suggest that 11beta-HSD1 limits acute inflammation. In contrast, 11beta-HSD2 plays no role in acute inflammatory responses in mice. Regulation of local 11beta-HSD1 expression and/or delivery of substrate may afford a novel approach for antiinflammatory therapy. |
