{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T12:27:49Z","timestamp":1768825669519,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Synthetic glucocorticoids (GC) are effective in the treatment of inflammatory diseases of the lung. However, long\u2010term use leads to severe side effects. Endogenous GC can be synthesized locally, either de novo from cholesterol in a 11\u03b2\u2010hydroxylase (<jats:italic>Cyp11b1<\/jats:italic>)\u2010dependent manner, or by reactivation from 11\u2010dehydrocorticosterone\/cortisone by 11\u03b2\u2010hydroxysteroid dehydrogenase 1 (<jats:italic>Hsd11b1<\/jats:italic>). We aimed to define the molecular pathways of endogenous GC synthesis along the respiratory tree to provide a basis for understanding how local GC synthesis contributes to tissue homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of steroidogenic enzymes in murine lung epithelium was analyzed by macroscopic and laser capture microdissection, followed by RT\u2010qPCR. Flow cytometry analysis was performed to identify the cellular source of steroidogenic enzymes. Additionally, the induction of steroidogenic enzyme expression in the lung was analyzed after lipopolysaccharide (LPS) injection. mRNA and protein expression of steroidogenic enzymes was confirmed in human lung tissue by RT\u2010qPCR and immunohistochemistry. Furthermore, GC synthesis was examined in ex vivo cultures of fresh tissue from mice and human lobectomy patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that the murine and human lung tissue differentially expresses synthesis pathway\u2010determining enzymes along the respiratory tree. We detected <jats:italic>Hsd11b1<\/jats:italic> expression in bronchial, alveolar, club and basal epithelial cells, whereas <jats:italic>Cyp11b1<\/jats:italic> expression was detectable only in tracheal epithelial cells of mice. Accordingly, de novo synthesis of bioactive GC occurred in the large conducting airways, whereas reactivation occurred everywhere along the respiratory tree. Strikingly, <jats:italic>Cyp11b1<\/jats:italic> but not <jats:italic>Hsd11b1<\/jats:italic> expression was enhanced in the trachea upon LPS injection in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report here the differential synthesis of bioactive GC along the murine and human respiratory tree. Thus, extra\u2010adrenal de novo GC synthesis and reactivation may differentially contribute to the regulation of immunological and inflammatory processes in the lung.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15765","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T14:43:33Z","timestamp":1683902613000},"page":"2428-2440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Glucocorticoids are differentially synthesized along the murine and human respiratory tree"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2470-681X","authenticated-orcid":false,"given":"Verena M.","family":"Merk","sequence":"first","affiliation":[{"name":"Biochemical Pharmacology, Department of Biology University of Konstanz  Konstanz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Renzulli","sequence":"additional","affiliation":[{"name":"Department of Surgery Cantonal Hospital M\u00fcnsterlingen  M\u00fcnsterlingen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Vrugt","sequence":"additional","affiliation":[{"name":"Institute of Pathology Cantonal Hospital M\u00fcnsterlingen  M\u00fcnsterlingen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achim","family":"Fleischmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology Cantonal Hospital M\u00fcnsterlingen  M\u00fcnsterlingen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-4712","authenticated-orcid":false,"given":"Thomas","family":"Brunner","sequence":"additional","affiliation":[{"name":"Biochemical Pharmacology, Department of Biology University of Konstanz  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