{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:43:04Z","timestamp":1772001784513,"version":"3.50.1"},"reference-count":70,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2499,"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":[[2002,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>IL\u201013 is an important mediator in inflammatory diseases such as asthma. IL\u201013 is mainly produced by T cells. However, signalling pathways leading to induction of this cytokine are not well\u2010characterized. We analysed the regulation of IL\u201013 in human peripheral blood mononuclear cells and CD4<jats:sup>+<\/jats:sup> T cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cyclosporine (CsA) and FK\u2010506 inhibited IL\u201013 synthesis, when cells were stimulated by TPA\/ionomycin. However, stimulation by \u03b1\u2010CD3\/\u03b1\u2010CD28 led to an enhanced IL\u201013 synthesis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NF\u2010\u03baB inhibitor N\u2010tosyl\u2010L\u2010lysine chloromethylketone (TLCK) inhibited IL\u201013 synthesis more effectively after TPA\/ionomycin stimulation. After \u03b1\u2010CD3\/\u03b1\u2010CD28 stimulation, only 300\u2003\u03bc<jats:sc>M<\/jats:sc> TLCK inhibited IL\u201013 synthesis. Dexamethasone inhibited IL\u201013 equally effective after \u03b1\u2010CD3\/\u03b1\u2010CD28 and TPA\/ionomycin stimulation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>p38 MAPK inhibitor SB203580 inhibited IL\u201013 synthesis only partially. MEK inhibitor U0126 inhibited TPA\/ionomycin induced IL\u201013 synthesis very effectively, whereas \u03b1\u2010CD3\/\u03b1\u2010CD28 stimulated IL\u201013 induction was resistant to this drug.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results were confirmed in purified CD4<jats:sup>+<\/jats:sup> T cells. In difference to PBMCs \u03b1\u2010CD3\/\u03b1\u2010CD28 stimulated IL\u201013 synthesis was effectively inhibited by CsA, FK\u2010506 and U0126.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Therefore U0126 was tested in an animal model of allergic asthma. We could demonstrate for the first time that inhibition of the MEK\u2003\u2013\u2003ERK cascade is a therapeutic option for asthma. Intraperitoneal administration of 10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> U0126 reduced lung eosinophilia in ovalbumin\u2010challenged Brown Norway rats by 44%.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results demonstrate that different signalling pathways are involved in regulating IL\u201013 synthesis in primary human T cells. Characterizing highly potent inhibitors of IL\u201013 synthesis can be exploited to identify new drugs to treat immunological diseases such as asthma.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>135<\/jats:bold>, 1915\u20131926; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704656\">10.1038\/sj.bjp.0704656<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704656","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:51:22Z","timestamp":1106949082000},"page":"1915-1926","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Regulation of IL\u201013 synthesis in human lymphocytes: implications for asthma therapy"],"prefix":"10.1111","volume":"135","author":[{"given":"Andreas","family":"Pahl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meixia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hildegard","family":"Kuss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istvan","family":"Szelenyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kay","family":"Brune","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01749-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200012)30:12<3645::AID-IMMU3645>3.0.CO;2-#"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/6.3.225"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:23:2-3:179"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-1878(200007)22:7<646::AID-BIES7>3.0.CO;2-9"},{"key":"e_1_2_7_7_1","first-page":"637","article-title":"Role of interleukin\u201013 in innate and adaptive immunity","volume":"47","author":"BRUBAKER J.O.","year":"2001","journal-title":"Cell. 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