Projects per year
Endogenous glucocorticoid action within cells is enhanced by prereceptor metabolism by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts intrinsically inert cortisone and 11-dehydrocorticosterone into active cortisol and corticosterone, respectively. 11β-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, 11β-HSD1-deficient mice show enhanced recruitment of inflammatory cells and delayed acquisition of macrophage phagocytic capacity. However, the key cells in which 11β-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 11β-HSD1 and show dynamic regulation of 11β-HSD1 in these cells during an inflammatory response. Flow cytometry showed high expression of 11β-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 11β-HSD1 activity in peritoneal cells, consistent with neutrophils being the predominant 11β-HSD1 expressing cell type at this time. Similar to genetic deficiency in 11β-HSD1, acute inhibition of 11β-HSD1 activity during thioglycollate-induced peritonitis augmented inflammatory cell recruitment to the peritoneum. These data suggest that neutrophil 11β-HSD1 increases during inflammation to contribute to the restraining effect of glucocorticoids upon neutrophil-mediated inflammation. In human neutrophils, lipopolysaccharide activation increased 11β-HSD1 expression, suggesting the antiinflammatory effects of 11β-HSD1 in neutrophils may be conserved in humans.
|Number of pages||9|
|Early online date||4 May 2016|
|Publication status||E-pub ahead of print - 4 May 2016|
FingerprintDive into the research topics of '11β-Hydroxysteroid Dehydrogenase type 1 is expressed in neutrophils and restrains an inflammatory response in male mice'. Together they form a unique fingerprint.
- 5 Finished
The role of cyclin-dependent kinase-9 inhibition in promoting the resolution of chronic inflammation
1/05/13 → 30/10/19
Edinburgh Clinical Academic Track (ECAT) training Programme - Dr Christopher Lucas
1/08/10 → 31/07/13
How does 11B-hydroxysteriod dehydrogenase type 1 limit inflammation.
Chapman, K., Gray, M., Savill, J. & Seckl, J.
1/10/08 → 30/04/12
- 1 Article
Getting to the heart of intracellular glucocorticoid regeneration: 11β-HSD1 in the myocardiumGray, G., White, C. I., Castellan, R. F. P., McSweeney, S. J. & Chapman, K., 1 Jan 2017, In: Journal of molecular endocrinology. 58, 1, p. R1-R13 13 p.
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile
- College of Medicine and Veterinary Medicine - Regius Chair of Medical Science
Person: Academic: Research Active