Macrophage 11?-HSD-1 deficiency promotes inflammatory angiogenesis.

ABSTRACT: 11?-Hydroxysteroid dehydrogenase-1 (11?-HSD1) predominantly converts inert glucocorticoids into active forms, thereby contributing to intracellular glucocorticoid levels. 11?-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 11?-HSD1 deficiency or inhibition. However, 11?-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 11?-HSD1 have not been characterised. Here, we generated Hsd11b1^MKO mice with LysM-Cre mediated deletion of Hsd11b1 to investigate whether 11?-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 11?-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, 11?-HSD1 deficiency in myeloid phagocytes promotes angiogenesis. Targeting 11?-HSD1 in macrophages may be beneficial in tissue repair.

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC5574305 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature