{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:03:16Z","timestamp":1790532196418,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The alkaloid narciclasine has been characterized extensively as an anticancer compound. Accumulating evidence suggests that narciclasine has anti\u2010inflammatory potential; however, the underlying mechanism remains poorly understood. We hypothesized that narciclasine affects the activation of endothelial cells (ECs), a hallmark of inflammatory processes, which is a prerequisite for leukocyte\u2010EC interaction. Thus, we aimed to investigate narciclasine's action on this process\n                    <jats:italic>in vivo<\/jats:italic>\n                    and to analyze the underlying mechanisms\n                    <jats:italic>in vitro<\/jats:italic>\n                    . In a murine peritonitis model, narciclasine reduced leukocyte infiltration, proinflammatory cytokine expression, and inflammation\u2010associated abdominal pain. Moreover, narciclasine decreased rolling and blocked adhesion and transmigration of leukocytes\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In cultured ECs, narciclasine inhibited the expression of cell adhesion molecules intercellular adhesion molecule\u20101, vascular cell adhesion molecule\u20101, and E\u2010selectin and blocked crucial steps of the NF\u2010\u03baB activation cascade: NF\u2010\u03baB promotor activity, p65 nuclear translocation, inhibitor of \u03baB \u03b1 (I\u03baB\u03b1*) phosphorylation and degradation, and I\u03baB\u03b1* kinase \u03b2 and TGF\u2010\u03b2\u2013activated kinase 1 phosphorylation. Interestingly, these effects were based on the narciclasine\u2010triggered loss of TNF receptor 1 (TNFR1). Our study highlights narciclasine as an interesting anti\u2010inflammatory compound that effectively inhibits the interaction of leukocytes with ECs by blocking endothelial activation processes. Most importantly, we showed that the observed inhibitory action of narciclasine on TNF\u2010triggered signaling pathways is based on the loss of TNFR1.\u2014Stark, A., Schwenk, R., Wack, G., Zuchtriegel, G., Hatemler, M. G., Br\u00e4utigam, J., Schmidtko, A., Reichel, C. A., Bischoff, I., F\u00fcrst, R. Narciclasine exerts antiinflammatory actions by blocking leukocyte\u2013endothelial cell interactions and down\u2010regulation of the endothelial TNF receptor 1. FASEB J. 33, 8771\u20138781 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802440r","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T14:17:50Z","timestamp":1556115470000},"page":"8771-8781","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Narciclasine exerts anti\u2010inflammatory actions by blocking leukocyte\u2013endothelial cell interactions and down\u2010regulation of the endothelial TNF receptor 1"],"prefix":"10.1096","volume":"33","author":[{"given":"Anna","family":"Stark","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Biology Goethe University Frankfurt  Frankfurt 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