KIT | KIT-Bibliothek | Impressum | Datenschutz

A Zebrafish Drug-Repurposing Screen Reveals sGC-Dependent and sGC-Independent Pro-Inflammatory Activities of Nitric Oxide

Wittmann, C. 1; Reischl, M. 2; Shah, A. H. 1; Kronfuss, E. 1; Mikut, R. ORCID iD icon 2; Liebel, U. 1; Grabher, C. 1
1 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)
2 Institut für Angewandte Informatik (IAI), Karlsruher Institut für Technologie (KIT)


Tissue injury and infection trigger innate immune responses. However, dysregulation may result in chronic inflammation and is commonly treated with corticosteroids and non-steroidal anti-inflammatory drugs. Unfortunately, long-term administration of both therapeutic classes can cause unwanted side effects. To identify alternative immune-modulatory compounds we have previously established a novel screening method using zebrafish larvae. Using this method we here present results of an in vivo high-content drug-repurposing screen, identifying 63 potent anti-inflammatory drugs that are in clinical use for other indications. Our approach reveals a novel pro-inflammatory role of nitric oxide. Nitric oxide affects leukocyte recruitment upon peripheral sensory nervous system or epithelial injury in zebrafish larvae both via soluble guanylate cyclase and in a soluble guanylate cyclase -independent manner through protein S-nitrosylation. Together, we show that our screening method can help to identify novel immune-modulatory activities and provide new mechanistic insights into the regulation of inflammatory processes.

Volltext §
DOI: 10.5445/IR/1000050815
DOI: 10.1371/journal.pone.0137286
Zitationen: 15
Web of Science
Zitationen: 14
Zitationen: 17
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Informatik (IAI)
Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2015
Sprache Englisch
Identifikator ISSN: 1932-6203
KITopen-ID: 1000050815
HGF-Programm 47.01.02 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. IAI
Erschienen in PLoS one
Verlag Public Library of Science (PLoS)
Band 10
Heft 10
Seiten Art.Nr.: e0137286
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Nachgewiesen in Scopus
Web of Science
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft
KITopen Landing Page