11β-Hydroxysteroid Dehydrogenase Type 1, But Not Type 2, Deficiency Worsens Acute Inflammation and Experimental Arthritis in Mice
| Autor: | Mohini Gray, John Savill, Karen E. Chapman, Deborah A. Sawatzky, David G. Brownstein, Agnes E. Coutinho, Donald Salter, Spike Clay, James S. Gilmour, Jonathan R. Seckl |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Peritonitis Arthritis Inflammation Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Immune system 11β-hydroxysteroid dehydrogenase type 1 Corticosterone 11-beta-Hydroxysteroid Dehydrogenase Type 2 Internal medicine 11-beta-Hydroxysteroid Dehydrogenase Type 1 medicine Animals Pleurisy 030304 developmental biology Mice Knockout 0303 health sciences biology medicine.disease Arthritis Experimental 3. Good health Mice Inbred C57BL chemistry Acute Disease biology.protein Joints Cortisone medicine.symptom Glucocorticoids-CRH-ACTH-Adrenal hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Glucocorticoid medicine.drug |
| Zdroj: | Endocrinology Coutinho, A E, Gray, M, Brownstein, D G, Salter, D M, Sawatzky, D A, Clay, S, Gilmour, J S, Seckl, J R, Savill, J S & Chapman, K E 2012, ' 11β-Hydroxysteroid Dehydrogenase Type 1, But Not Type 2, Deficiency Worsens Acute Inflammation and Experimental Arthritis in Mice ', Endocrinology, vol. 153, no. 1, pp. 234-240 . https://doi.org/10.1210/en.2011-1398 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2011-1398 |
| Popis: | 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 11β-hydroxysteroid dehydrogenase (11β-HSD). In vivo, 11β-HSD1 catalyzes the reduction of inactive cortisone or 11-dehydrocorticosterone into active cortisol or corticosterone, respectively, thereby increasing intracellular glucocorticoid levels. 11β-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, 11β-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 11β-HSD2 deficiency. In a distinct model of inflammation, thioglycollate-induced sterile peritonitis, 11β-HSD1-deficient mice had more inflammatory cells in the peritoneum, but again 11β-HSD2-deficient mice did not differ from controls. Additionally, compared with control mice, 11β-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 11β-HSD1 limits acute inflammation. In contrast, 11β-HSD2 plays no role in acute inflammatory responses in mice. Regulation of local 11β-HSD1 expression and/or delivery of substrate may afford a novel approach for antiinflammatory therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|