| First Author | Coutinho AE | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 7 | Pages | 2928-36 |
| PubMed ID | 27145012 | Mgi Jnum | J:239730 |
| Mgi Id | MGI:5829546 | Doi | 10.1210/en.2016-1118 |
| Citation | Coutinho AE, et al. (2016) 11beta-Hydroxysteroid Dehydrogenase Type 1 Is Expressed in Neutrophils and Restrains an Inflammatory Response in Male Mice. Endocrinology 157(7):2928-36 |
| abstractText | Endogenous glucocorticoid action within cells is enhanced by prereceptor metabolism by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which converts intrinsically inert cortisone and 11-dehydrocorticosterone into active cortisol and corticosterone, respectively. 11beta-HSD1 is highly expressed in immune cells elicited to the mouse peritoneum during thioglycollate-induced peritonitis and is down-regulated as the inflammation resolves. During inflammation, 11beta-HSD1-deficient mice show enhanced recruitment of inflammatory cells and delayed acquisition of macrophage phagocytic capacity. However, the key cells in which 11beta-HSD1 exerts these effects remain unknown. Here we have identified neutrophils (CD11b(+),Ly6G(+),7/4(+) cells) as the thioglycollate-recruited cells that most highly express 11beta-HSD1 and show dynamic regulation of 11beta-HSD1 in these cells during an inflammatory response. Flow cytometry showed high expression of 11beta-HSD1 in peritoneal neutrophils early during inflammation, declining at later states. In contrast, expression in blood neutrophils continued to increase during inflammation. Ablation of monocytes/macrophages by treatment of CD11b-diphtheria-toxin receptor transgenic mice with diphtheria toxin prior to thioglycollate injection had no significant effect on 11beta-HSD1 activity in peritoneal cells, consistent with neutrophils being the predominant 11beta-HSD1 expressing cell type at this time. Similar to genetic deficiency in 11beta-HSD1, acute inhibition of 11beta-HSD1 activity during thioglycollate-induced peritonitis augmented inflammatory cell recruitment to the peritoneum. These data suggest that neutrophil 11beta-HSD1 increases during inflammation to contribute to the restraining effect of glucocorticoids upon neutrophil-mediated inflammation. In human neutrophils, lipopolysaccharide activation increased 11beta-HSD1 expression, suggesting the antiinflammatory effects of 11beta-HSD1 in neutrophils may be conserved in humans. |
