{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:49:34Z","timestamp":1791089374715,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3469,"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":[[1999,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Endothelial cell damage in glomeruli and kidney arterioles appears to play a pivotal role in glomerular inflammatory diseases. Glomerular endothelial cells, a specialized microvascular cell type involved in the regulation of glomerular ultrafiltration, die by apoptosis in response to tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), TNF\u2010\u03b1\/basic fibroblast growth factor (bFGF), TNF\u2010\u03b1\/cycloheximide, and bacterial lipopolysaccharide (LPS). Apoptotic cell death is characterized by extensive DNA cleavage, DNA ladder formation, and characteristic morphological alterations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In search for apoptosis\u2010preventing signals, we identified glucocorticoids as potent death preventing factors. Co\u2010treatment of cells with 10 n<jats:sc>M<\/jats:sc> dexamethasone and TNF\u2010\u03b1, TNF\u2010\u03b1\/bFGF, TNF\u2010\u03b1\/cycloheximide, or LPS blocked roughly 90% of apoptotic cell death in glomerular endothelial cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Similarly to dexamethasone (TNF\u2010\u03b1\u2010 and LPS\u2010induced apoptosis are prevented with IC<jats:sub>50<\/jats:sub> values of 0.8 and 0.9\u2003n<jats:sc>M<\/jats:sc>, respectively), other synthetic and natural forms of glucocorticoids, such as fluocinolone, prednisolone, hydrocortisone, and corticosterone potently inhibited cell death with IC<jats:sub>50<\/jats:sub> values of 0.2, 6, 50 and 1000\u2003n<jats:sc>M<\/jats:sc>, for TNF\u2010\u03b1 and 0.7, 8, 100 and 500\u2003n<jats:sc>M<\/jats:sc> for LPS, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Apart from glucocorticoids, mineralocorticoids such as aldosterone also blocked TNF\u2010\u03b1\/LPS\u2010induced apoptosis (IC<jats:sub>50<\/jats:sub> \u223c500\u2003n<jats:sc>M<\/jats:sc> for TNF\u2010\u03b1 and \u223c500\u2003n<jats:sc>M<\/jats:sc> for LPS), whereas sex hormones, i.e. \u03b2\u2010estradiol and testosterone remained without effect.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The protective effect of glucocorticoids (and mineralocorticoids) required glucocorticoid receptor binding as it could be antagonized by the glucocorticoid receptor antagonist RU\u2010486. Concerning TNF\u2010\u03b1 and LPS signal transduction, we found that dexamethasone efficiently prevented TNF\u2010\u03b1\u2010 and LPS\u2010induced activation of caspase\u20103\u2010like proteases. Therefore, we postulate inhibitory mechanisms upstream of terminal death pathways.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>127<\/jats:bold>, 1633\u20131640; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702726\">10.1038\/sj.bjp.0702726<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702726","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:21:01Z","timestamp":1106943661000},"page":"1633-1640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Glucocorticoids potently block tumour necrosis factor\u2010\u03b1\u2010 and lipopolysaccharide\u2010induced apoptotic cell death in bovine glomerular endothelial cells upstream of caspase 3 activation"],"prefix":"10.1111","volume":"127","author":[{"given":"Udo K","family":"Me\u00dfmer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gundula","family":"Winkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena A","family":"Briner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Pfeilschifter","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":"10.1126\/science.270.5234.286"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1989.256.1.C182"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.90"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1989.98"},{"key":"e_1_2_7_6_1","first-page":"419","article-title":"Tumor necrosis factor induces glomerular damage in the rabbit","volume":"134","author":"BERTANI T.","year":"1989","journal-title":"Am. 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