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

Wittmann, C.; Reischl, M.; Shah, A.H.; Kronfuss, E.; Mikut, R.; Liebel, U.; Grabher, C.

Abstract:
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.

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Volltext §
DOI: 10.5445/IR/1000050815
Originalveröffentlichung
DOI: 10.1371/journal.pone.0137286
Scopus
Zitationen: 9
Web of Science
Zitationen: 9
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Institut für Angewandte Informatik (IAI)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2015
Sprache Englisch
Identifikator ISSN: 1932-6203
urn:nbn:de:swb:90-508153
KITopen-ID: 1000050815
HGF-Programm 47.01.02 (POF III, LK 01)
Biol.Netzwerke u.Synth.Regulat. IAI
Erschienen in PLoS one
Band 10
Heft 10
Seiten Art.Nr.: e0137286
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Nachgewiesen in Web of Science
Scopus
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