{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:17:26Z","timestamp":1790371046302,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[1994,6,1]],"date-time":"1994-06-01T00:00:00Z","timestamp":770428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interleukin (IL)-6 is a pleiotropic cytokine produced by a wide variety of cells including fibroblasts, macrophages, endothelial cells, and T and B lymphocytes. Regulated IL-6 production is an important part of normal biologic homeostasis, and abnormal IL-6 production has been associated with a large number of diseases including asthma and lung allograft rejection. Glucocorticoids are potent anti-inflammatory agents that are widely used to suppress pulmonary inflammation. To further understand the mechanisms underlying this inhibition, we determined whether glucocorticoid compounds regulate human lung fibroblast IL-6 production and characterized the mechanisms of the effects that were noted. These studies demonstrate that glucocorticoids inhibit IL-1-induced IL-6 production in a dose-dependent fashion. A greater than 95% decrease in IL-6 production was seen with 10(-6) and 10(-7) M dexamethasone, prednisolone, and hydrocortisone, and IC50 values for these agents were approximately 5 x 10(-10), 5 x 10(-9), and 10(-8) M, respectively. mRNA analysis demonstrated that these alterations in protein production were associated with proportionate decreases in IL-6 mRNA accumulation, and that this suppression of IL-6 mRNA could be reversed by the glucocorticoid receptor antagonist RU 486. Nuclear run-on studies demonstrated that glucocorticoids inhibit-IL-1-induced IL-6 gene transcription. However, the magnitude of this effect could not fully account for the potency of the glucocorticoid-induced alterations in IL-6 mRNA accumulation and protein production since 10(-6) M dexamethasone caused only a 50% decrease in IL-1-induced IL-6 gene transcription.(ABSTRACT TRUNCATED AT 250 WORDS)<\/jats:p>","DOI":"10.1165\/ajrcmb.10.6.7516173","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T22:29:24Z","timestamp":1365028164000},"page":"643-650","source":"Crossref","is-referenced-by-count":48,"title":["Glucocorticoid Inhibition of Interleukin-1-Induced Interleukin-6 Production by Human Lung Fibroblasts: Evidence for Transcriptional and Post-Transcriptional Regulatory Mechanisms"],"prefix":"10.1093","volume":"10","author":[{"given":"R J","family":"Zitnik","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510-8057"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N L","family":"Whiting","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510-8057"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510-8057"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1994,6,1]]},"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/10\/6\/643\/67373099\/ajrcmb_10_6_643.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/10\/6\/643\/67373099\/ajrcmb_10_6_643.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:48:47Z","timestamp":1773722927000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/10\/6\/643\/8525222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,6,1]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[1994,6,1]]},"published-print":{"date-parts":[[1994,6,1]]}},"URL":"https:\/\/doi.org\/10.1165\/ajrcmb.10.6.7516173","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1994,6]]},"published":{"date-parts":[[1994,6,1]]}}}