{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:05:11Z","timestamp":1791223511368,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1004,"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":[[2006,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Spironolactone (SPIR) binds to cytoplasmic mineralocorticoid receptors (MR) and functions as an aldosterone antagonist. Recently, the drug was shown to have an early suppressive effect on several immunoactive and proinflammatory cytokines.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>To elucidate the mechanism behind this, the four MR\u2010binding steroids SPIR, canrenone, 7<jats:italic>\u03b1<\/jats:italic>\u2010thiomethyl\u2010spironolactone and aldosterone (ALDO) were investigated for effects on lipopolysaccharide\u2010 and phytohemagglutinin\u2010A\u2010activated human blood mononuclear cells. Gene expression was examined after 4\u2003h using microarrays, and SPIR affected 1018 transcripts of the (=) 22,000 probed. In contrast, the SPIR\u2010related steroids affected 17 or fewer transcripts. Combining SPIR and ALDO resulted in 940 affected transcripts, indicating that SPIR has an early gene\u2010regulatory effect independent of MR.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The affected genes encode a large number of signalling proteins and receptors, including immunoinflammatory response genes and apoptosis and antiapoptosis genes. Apoptosis was evident in CD3\u2010, CD14\u2010 and CD19\u2010positive cells, but only after 18\u2003h of exposure to SPIR.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The transcriptional network involving the differentially regulated genes was examined and the results indicate that SPIR affects genes controlled by the transcription factors NF\u2010<jats:italic>\u03ba<\/jats:italic>B, CEBP<jats:italic>\u03b2<\/jats:italic> and MYC.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These observations provide new insight into the non\u2010MR\u2010mediated effects of SPIR.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2006) <jats:bold>148<\/jats:bold>, 46\u201353. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706700\">10.1038\/sj.bjp.0706700<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706700","type":"journal-article","created":{"date-parts":[[2006,3,6]],"date-time":"2006-03-06T16:03:05Z","timestamp":1141660985000},"page":"46-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Effects of spironolactone on human blood mononuclear cells: mineralocorticoid receptor independent effects on gene expression and late apoptosis induction"],"prefix":"10.1111","volume":"148","author":[{"given":"S\u00f8ren Ulrik Salling","family":"S\u00f8nder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Mikkelsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Rieneck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris Juul","family":"Hedegaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Bendtzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000173953"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5234.286"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","unstructured":"BENDTZEN K. HANSEN P.R. RIENECK K.&THE SPIRONOLACTONE\/ARTHRITIS STUDY GROUP. (2003).Spironolactone inhibits production of proinflammatory cytokines including tumor necrosis factor a and interferon\u2010g and has potential in the treatment of arthritis.Clin. Exp. 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