{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:11:47Z","timestamp":1773673907815,"version":"3.50.1"},"reference-count":34,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T00:00:00Z","timestamp":1479859200000},"content-version":"vor","delay-in-days":145,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:p>Endogenous glucocorticoid action within cells is enhanced by prereceptor metabolism by 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1), which converts intrinsically inert cortisone and 11-dehydrocorticosterone into active cortisol and corticosterone, respectively. 11\u03b2-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, 11\u03b2-HSD1-deficient mice show enhanced recruitment of inflammatory cells and delayed acquisition of macrophage phagocytic capacity. However, the key cells in which 11\u03b2-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 11\u03b2-HSD1 and show dynamic regulation of 11\u03b2-HSD1 in these cells during an inflammatory response. Flow cytometry showed high expression of 11\u03b2-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 11\u03b2-HSD1 activity in peritoneal cells, consistent with neutrophils being the predominant 11\u03b2-HSD1 expressing cell type at this time. Similar to genetic deficiency in 11\u03b2-HSD1, acute inhibition of 11\u03b2-HSD1 activity during thioglycollate-induced peritonitis augmented inflammatory cell recruitment to the peritoneum. These data suggest that neutrophil 11\u03b2-HSD1 increases during inflammation to contribute to the restraining effect of glucocorticoids upon neutrophil-mediated inflammation. In human neutrophils, lipopolysaccharide activation increased 11\u03b2-HSD1 expression, suggesting the antiinflammatory effects of 11\u03b2-HSD1 in neutrophils may be conserved in humans.<\/jats:p>","DOI":"10.1210\/en.2016-1118","type":"journal-article","created":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T17:57:00Z","timestamp":1462384620000},"page":"2928-2936","source":"Crossref","is-referenced-by-count":25,"title":["11\u03b2-Hydroxysteroid Dehydrogenase Type 1 Is Expressed in Neutrophils and Restrains an Inflammatory Response in Male Mice"],"prefix":"10.1210","volume":"157","author":[{"given":"Agnes E.","family":"Coutinho","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiina M. J.","family":"Kipari","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenguang","family":"Zhang","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina L.","family":"Esteves","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher D.","family":"Lucas","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Inflammation Research (A.E.C., C.D.L., J.S.G., J.H., J.S.S., A.G.R.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James S.","family":"Gilmour","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott P.","family":"Webster","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian R.","family":"Walker","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Hughes","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Inflammation Research (A.E.C., C.D.L., J.S.G., J.H., J.S.S., A.G.R.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S.","family":"Savill","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Inflammation Research (A.E.C., C.D.L., J.S.G., J.H., J.S.S., A.G.R.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan R.","family":"Seckl","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano G.","family":"Rossi","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"},{"name":"Medical Research Council Centre for Inflammation Research (A.E.C., C.D.L., J.S.G., J.H., J.S.S., A.G.R.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen E.","family":"Chapman","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular Science (A.E.C., T.M.J.K., Z.Z., C.L.E., J.S.G., S.P.W., B.R.W., J.R.S., K.E.C.), Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071612114327800_B1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.chom.2014.04.011","article-title":"The balancing act of neutrophils","volume":"15","author":"Bardoel","year":"2014","journal-title":"Cell Host Microbe"},{"key":"2020071612114327800_B2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2010.04.005","article-title":"The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights","volume":"335","author":"Coutinho","year":"2011","journal-title":"Mol Cell Endocrinol"},{"key":"2020071612114327800_B3","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nm.3599","article-title":"An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action","volume":"20","author":"Gibbs","year":"2014","journal-title":"Nat Med"},{"key":"2020071612114327800_B4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1749-6632.2003.tb03141.x","article-title":"Hypothalamo-pituitary-adrenal axis and chronic immune activation","volume":"992","author":"Harbuz","year":"2003","journal-title":"Ann NY Acad Sci"},{"key":"2020071612114327800_B5","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1006\/cimm.1998.1293","article-title":"Glucocorticoid receptors are differentially expressed in the cells and tissues of the immune system","volume":"186","author":"Miller","year":"1998","journal-title":"Cell Immunol"},{"key":"2020071612114327800_B6","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1084\/jem.193.5.585","article-title":"High constitutive glucocorticoid receptor \u03b2 in human neutrophils enables them to reduce their spontaneous rate of cell death in response to corticosteroids","volume":"193","author":"Strickland","year":"2001","journal-title":"J Exp Med"},{"key":"2020071612114327800_B7","doi-asserted-by":"crossref","first-page":"e44606","DOI":"10.1371\/journal.pone.0044606","article-title":"Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids","volume":"7","author":"Hirsch","year":"2012","journal-title":"PLoS One"},{"key":"2020071612114327800_B8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1159\/000337801","article-title":"Neutrophilic inflammation in severe asthma","volume":"158","author":"Nakagome","year":"2012","journal-title":"Int Arch Allergy Immunol"},{"key":"2020071612114327800_B9","doi-asserted-by":"crossref","first-page":"4422","DOI":"10.4049\/jimmunol.156.11.4422","article-title":"Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes","volume":"156","author":"Meagher","year":"1996","journal-title":"J Immunol"},{"key":"2020071612114327800_B10","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1189\/jlb.0912462","article-title":"Oxygen levels determine the ability of glucocorticoids to influence neutrophil survival in inflammatory environments","volume":"94","author":"Marwick","year":"2013","journal-title":"J Leukoc Biol"},{"key":"2020071612114327800_B11","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1152\/physrev.00020.2012","article-title":"11\u03b2-Hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action","volume":"93","author":"Chapman","year":"2013","journal-title":"Physiol Rev"},{"key":"2020071612114327800_B12","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/j.leukres.2011.07.002","article-title":"Expression of 11\u03b2-hydroxysteroid dehydrogenase 2 contributes to glucocorticoid resistance in lymphoblastic leukemia cell lines","volume":"35","author":"Sai","year":"2011","journal-title":"Leuk Res"},{"key":"2020071612114327800_B13","doi-asserted-by":"crossref","first-page":"e67067","DOI":"10.1371\/journal.pone.0067067","article-title":"Down-regulation of 11\u03b2-hydroxysteroid dehydrogenase type 2 by bortezomib sensitizes Jurkat leukemia T cells against glucocorticoid-induced apoptosis","volume":"8","author":"Tao","year":"2013","journal-title":"PLoS One"},{"key":"2020071612114327800_B14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.mce.2008.09.031","article-title":"The role and regulation of 11\u03b2-hydroxysteroid dehydrogenase type 1 in the inflammatory response","volume":"301","author":"Chapman","year":"2009","journal-title":"Mol Cell Endocrinol"},{"key":"2020071612114327800_B15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jsbmb.2013.02.002","article-title":"Changing glucocorticoid action: 11\u03b2-hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation","volume":"137","author":"Chapman","year":"2013","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071612114327800_B16","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1210\/endo.142.1.7887","article-title":"Intracellular regeneration of glucocorticoids by 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2-HSD)-1 plays a key role in regulation of the hypothalamic-pituitary-adrenal axis: analysis of 11\u03b2-HSD-1 deficient mice","volume":"142","author":"Harris","year":"2001","journal-title":"Endocrinology"},{"key":"2020071612114327800_B17","doi-asserted-by":"crossref","first-page":"E2482","DOI":"10.1073\/pnas.1323681111","article-title":"11\u03b2-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess","volume":"111","author":"Morgan","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612114327800_B18","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/j.febslet.2008.04.045","article-title":"Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human neutrophil granulocytes","volume":"582","author":"Kardon","year":"2008","journal-title":"FEBS Lett"},{"key":"2020071612114327800_B19","doi-asserted-by":"crossref","first-page":"7605","DOI":"10.4049\/jimmunol.176.12.7605","article-title":"Local amplification of glucocorticoids by 11\u03b2-hydroxysteroid dehydrogenase type 1 promotes macrophage phagocytosis of apoptotic leukocytes","volume":"176","author":"Gilmour","year":"2006","journal-title":"J Immunol"},{"key":"2020071612114327800_B20","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1210\/en.2011-1398","article-title":"11\u03b2-Hydroxysteroid dehydrogenase type 1, but not type 2, deficiency worsens acute inflammation and experimental arthritis in mice","volume":"153","author":"Coutinho","year":"2012","journal-title":"Endocrinology"},{"key":"2020071612114327800_B21","doi-asserted-by":"crossref","first-page":"11576","DOI":"10.1021\/ac402777k","article-title":"Mass spectrometry imaging for dissecting steroid intracrinology within target tissues","volume":"85","author":"Cobice","year":"2013","journal-title":"Anal Chem"},{"key":"2020071612114327800_B22","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/mi.2013.102","article-title":"Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung","volume":"7","author":"Lucas","year":"2014","journal-title":"Mucosal Immunol"},{"key":"2020071612114327800_B23","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1210\/en.2007-1028","article-title":"Preadipocyte 11\u03b2-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in vivo","volume":"149","author":"De Sousa Peixoto","year":"2008","journal-title":"Endocrinology"},{"key":"2020071612114327800_B24","doi-asserted-by":"crossref","first-page":"e54640","DOI":"10.1371\/journal.pone.0054640","article-title":"Mast cells express 11\u03b2-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation","volume":"8","author":"Coutinho","year":"2013","journal-title":"PLoS One"},{"key":"2020071612114327800_B25","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.4049\/jimmunol.174.4.2336","article-title":"Conditional macrophage ablation demonstrates that resident macrophages initiate acute peritoneal inflammation","volume":"174","author":"Cailhier","year":"2005","journal-title":"J Immunol"},{"key":"2020071612114327800_B26","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1210\/me.2007-0489","article-title":"Glucocorticoid regulation of the promoter of 11\u03b2-hydroxysteroid dehydrogenase type 1 is indirect and requires C\/EBP\u03b2","volume":"22","author":"Sai","year":"2008","journal-title":"Mol Endocrinol"},{"key":"2020071612114327800_B27","doi-asserted-by":"crossref","first-page":"e75874","DOI":"10.1371\/journal.pone.0075874","article-title":"Pro-inflammatory cytokine induction of 11\u03b2-hydroxysteroid dehydrogenase type 1 in A549 cells requires phosphorylation of C\/EBP\u03b2 at Thr235","volume":"8","author":"Esteves","year":"2013","journal-title":"PLoS One"},{"key":"2020071612114327800_B28","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1182\/blood.V78.4.1105.1105","article-title":"Membrane surface antigen expression on neutrophils: a reappraisal of the use of surface markers for neutrophil activation","volume":"78","author":"Kuijpers","year":"1991","journal-title":"Blood"},{"key":"2020071612114327800_B29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1189\/jlb.1103552","article-title":"Annexin 1 and the biology of the neutrophil","volume":"76","author":"Perretti","year":"2004","journal-title":"J Leukoc Biol"},{"key":"2020071612114327800_B30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/cvr\/cvq149","article-title":"Improved heart function follows enhanced inflammatory cell recruitment and angiogenesis in 11\u03b2-HSD1-deficient mice post-MI","volume":"88","author":"McSweeney","year":"2010","journal-title":"Cardiovasc Res"},{"key":"2020071612114327800_B31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1213\/00000539-199407000-00006","article-title":"Glucocorticoids blunt neutrophil CD11b surface glycoprotein upregulation during cardiopulmonary bypass in humans","volume":"79","author":"Hill","year":"1994","journal-title":"Anesth Analg"},{"key":"2020071612114327800_B32","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1677\/jme.1.01718","article-title":"Hexose-6-phosphate dehydrogenase confers oxo-reductase activity upon 11\u03b2-hydroxysteroid dehydrogenase type 1","volume":"34","author":"Bujalska","year":"2005","journal-title":"J Mol Endocrinol"},{"key":"2020071612114327800_B33","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/ATVBAHA.111.241364","article-title":"Peroxisome proliferator activated receptor-\u03b3 activation induces 11\u03b2-hydroxysteroid dehydrogenase type 1 activity in human alternative macrophages","volume":"32","author":"Chinetti-Gbaguidi","year":"2012","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020071612114327800_B34","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s40265-013-0112-5","article-title":"11\u03b2-HSD1 inhibitors for the treatment of type 2 diabetes and cardiovascular disease","volume":"73","author":"Anderson","year":"2013","journal-title":"Drugs"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/157\/7\/2928\/20218290\/endo2928.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/157\/7\/2928\/20218290\/endo2928.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T22:21:07Z","timestamp":1692310867000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/157\/7\/2928\/2423022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,1]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2016-1118","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,1]]}}}