{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:43:35Z","timestamp":1788381815078,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2015,10,17]],"date-time":"2015-10-17T00:00:00Z","timestamp":1445040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The anti\u2010inflammatory and immunomodulatory effects of macrolides include the ability to decrease mucus secretion and inhibit inflammatory mediators in chronic rhinosinusitis. Nevertheless, their mechanisms of action remain to be determined. Here we have investigated the effects of macrolide antibiotics (clarithromycin, azithromycin and josamycin; representating the 14\u2010, 15\u2010 and 16\u2010membered macrolides) on endogenous steroids in human sinonasal epithelial cells and mouse nasal mucosa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The effects of macrolides on the expression of steroid\u2010converting enzymes [11\u03b2\u2010hydroxysteroid dehydrogenase (11\u03b2\u2010HSD1 and 11\u03b2\u2010HSD2)], steroid\u2010synthesizing enzymes (3\u03b2\u2010HSD, CYP21, CYP11B1 and CYP11A1) and cortisol levels were assessed in cultured human epithelial cells. In control and adrenalectomized mice , these enzymes and corticosterone levels were evaluated in nasal mucosa and serum after administration of macrolides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The expression levels of 3\u03b2\u2010HSD, CYP21, 11\u03b2\u2010HSD1 and CYP11B1 increased in human epithelial cells treated with clarithromycin and azithromycin, whereas the expression levels of 11\u03b2\u2010HSD2 and CYP11A1 were not affected. Josamycin had no effects on the expression of these enzymes. Cortisol levels increased in epithelial cells treated with clarithromycin or azithromycin. The expression of 3\u03b2\u2010HSD, CYP11A1, CYP21, CYP11B1 and 11\u03b2\u2010HSD1 was upregulated in nasal mucosa of mice treated with clarithromycin or azithromycin, but not in adrenalectomized mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>This study provides evidence that 14\u2010 and 15\u2010membered macrolide antibiotics may affect the expression of steroid\u2010synthesizing and steroid\u2010converting enzymes in human sinonasal epithelial cells and mouse nasal mucosa, increasing the endogenous cortisol levels in sinonasal mucosa.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13273","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T05:41:16Z","timestamp":1438321276000},"page":"5083-5095","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Macrolides increase the expression of 11\u03b2\u2010hydroxysteroid dehydrogenase 1 in human sinonasal epithelium, contributing to glucocorticoid activation in sinonasal mucosa"],"prefix":"10.1111","volume":"172","author":[{"given":"Se Jin","family":"Park","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery, College of Medicine Korea University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Ho","family":"Kook","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery, College of Medicine Hallym University  Chuncheon Gangwon Do South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Kyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery, College of Medicine Korea University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung 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