| First Author | Zhang Z | Year | 2017 |
| Journal | J Endocrinol | Volume | 234 |
| Issue | 3 | Pages | 291-299 |
| PubMed ID | 28676523 | Mgi Jnum | J:271961 |
| Mgi Id | MGI:6282525 | Doi | 10.1530/JOE-17-0223 |
| Citation | Zhang Z, et al. (2017) Macrophage 11beta-HSD-1 deficiency promotes inflammatory angiogenesis. J Endocrinol 234(3):291-299 |
| abstractText | 11beta-Hydroxysteroid dehydrogenase-1 (11beta-HSD1) predominantly converts inert glucocorticoids into active forms, thereby contributing to intracellular glucocorticoid levels. 11beta-HSD1 is dynamically regulated during inflammation, including in macrophages where it regulates phagocytic capacity. The resolution of inflammation in some disease models including inflammatory arthritis is impaired by 11beta-HSD1 deficiency or inhibition. However, 11beta-HSD1 deficiency/inhibition also promotes angiogenesis, which is beneficial in mouse models of surgical wound healing, myocardial infarction or obesity. The cell types responsible for the anti-inflammatory and anti-angiogenic roles of 11beta-HSD1 have not been characterised. Here, we generated Hsd11b1(MKO) mice with LysM-Cre mediated deletion of Hsd11b1 to investigate whether 11beta-HSD1 deficiency in myeloid phagocytes is pro-angiogenic and/or affects the resolution of inflammation. Resolution of inflammatory K/BxN-induced arthritis was impaired in Hsd11b1(MKO) mice to a similar extent as in mice globally deficient in 11beta-HSD1. This was associated with >2-fold elevation in levels of the endothelial marker Cdh5 mRNA, suggesting increased angiogenesis in joints of Hsd11b1(MKO) mice following arthritis. A pro-angiogenic phenotype was confirmed by measuring angiogenesis in subcutaneously implanted polyurethane sponges, in which Hsd11b1(MKO) mice showed 20% greater vessel density than their littermate controls, associated with higher expression of Cdh5 Thus, 11beta-HSD1 deficiency in myeloid phagocytes promotes angiogenesis. Targeting 11beta-HSD1 in macrophages may be beneficial in tissue repair. |
