{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:58:31Z","timestamp":1773291511077,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2005,12,5]],"date-time":"2005-12-05T00:00:00Z","timestamp":1133740800000},"content-version":"vor","delay-in-days":2956,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1997,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The interleukin\u20101 receptor type I (IL\u20101RI) is associated with other proteins thus forming a complex system by which IL\u20101 exerts its various signals. The initiating event is still uncertain, but activation of a recently described receptor\u2010associated protein kinase is one of the earliest events detectable (Martin et al., <jats:italic>Eur. J. Immunol.<\/jats:italic> 1994. <jats:italic>24<\/jats:italic>: 1566). IL\u20101 signaling is commonly accompanied by oxidative processes and is thought to be subject to redox regulation. We therefore investigated whether the activation of the IL\u20101RI\u2010associated protein kinase could be a target for redox regulation and whether an altered activity of the kinase could influence IL\u20101\u2010mediated NF\u2010<jats:italic>x<\/jats:italic>B activation. A murine T cell line, EL4, was stimulated with IL\u20101 with and without pretreatment with different compounds known to influence the cellular redox status. Thiol modifying agents like diamide, menadione, pyrrolidine dithiocarbamate (PDTC), diethyl dithiocarbamate or phenylarsine oxide inhibited the IL\u20101\u2010induced activation of the IL\u20101RI\u2010associated protein kinase. N\u2010Acetylcysteine, \u03b1,\u03b1\u2032\u2010dipyridyl, aminotriazole or nitrofurantoin did not show any effect. The inhibition by PDTC was reversible unless glutathione synthesis was blocked by buthionine sulfoximine. The described conditions which inhibited or prevented the activation of the IL\u20101RI\u2010associated kinase similarly impaired the activation of NF\u2010<jats:italic>x<\/jats:italic>B in EL4 cells. From these observations we conclude that free thiols in the IL\u20101RI complex are essential for the activation of the IL\u20101RI\u2010associated protein kinase and that this process is mandatory for IL\u20101 signaling leading to NF\u2010<jats:italic>x<\/jats:italic>B activation.<\/jats:p>","DOI":"10.1002\/eji.1830271139","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T04:06:15Z","timestamp":1172808375000},"page":"3015-3021","source":"Crossref","is-referenced-by-count":24,"title":["Thiol modulation inhibits the interleukin (IL)\u20101\u2010mediated activation of an IL\u20101 receptor\u2010associated protein kinase and NF\u2010<i>x<\/i>B"],"prefix":"10.1002","volume":"27","author":[{"given":"Frank","family":"Tewes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaby\u2010Fleur","family":"B\u00f6l","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Brigelius\u2010Floh\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,5]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.136.1.143"},{"key":"e_1_2_1_3_2","first-page":"517","volume":"5","author":"Dinarello C. 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