{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:43:45Z","timestamp":1790775825346,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"38","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,9,20]]},"abstract":"<jats:p>\n                    Imatinib exerts potent antileukemic effects\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Despite its well known antitumor activity, the potential of imatinib for the treatment of inflammatory diseases remains elusive so far. Our current report provides strong evidence that imatinib has potent antiinflammatory effects. It potently inhibits LPS- and Con A-induced TNF-\u03b1 production by human myeloid cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    (peripheral blood mononuclear cells, CD14-selected monocytes, and monocyte-derived macrophages). Of note, the production of the antiinflammatory cytokine IL-10 was not significantly regulated by imatinib. In line with this observation, phosphorylation of I\u03baB and subsequent DNA binding of NF-\u03baB, which is critically involved in TNF-\u03b1, but not IL-10 expression, was reduced by imatinib. Using several murine models of acute hepatitis, we could corroborate our\n                    <jats:italic>in vitro<\/jats:italic>\n                    findings, as imatinib prevented macrophage- and TNF-\u03b1-dependent inflammatory damage of the liver induced by injection of either Con A or\n                    <jats:sc>d<\/jats:sc>\n                    -galactosamine\/LPS by inhibition of hepatic TNF-\u03b1 production. Of note,\n                    <jats:sc>d<\/jats:sc>\n                    -galactosamine\/TNF-induced hepatitis was not affected, showing that imatinib does not directly inhibit TNF-\u03b1-induced hepatocellular cell death. These findings suggest a potent antiinflammatory role of imatinib by modulation of TNF-\u03b1 production in monocytes\/macrophages. This observation might be of therapeutic value for the treatment of TNF-mediated diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0501758102","type":"journal-article","created":{"date-parts":[[2005,9,8]],"date-time":"2005-09-08T20:33:26Z","timestamp":1126211606000},"page":"13622-13627","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":115,"title":["The kinase inhibitor imatinib mesylate inhibits TNF-\u03b1 production\n                    <i>in vitro<\/i>\n                    and prevents TNF-dependent acute hepatic inflammation"],"prefix":"10.1073","volume":"102","author":[{"given":"Anna Maria","family":"Wolf","sequence":"first","affiliation":[{"name":"Departments of Gastroenterology and Hepatology, Hematology and Oncology, and Internal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Wolf","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology, Hematology and Oncology, and Internal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Rumpold","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology, Hematology and Oncology, and Internal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Ludwiczek","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology, Hematology and Oncology, and Internal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Enrich","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology, Hematology and Oncology, and Internal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guenther","family":"Gastl","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology, Hematology and Oncology, and Internal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guenter","family":"Weiss","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology, Hematology and Oncology, and Internal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Tilg","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology, Hematology and Oncology, and Internal Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,9,8]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.3.4"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.091301.131133"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0975"},{"key":"e_1_3_2_4_2","first-page":"2473","volume":"105","year":"2004","unstructured":"Seggewiss, R., Lore, K., Greiner, E., Magnusson, M. 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