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DOI: 10.5445/IR/1000050815

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.

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.

Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Institut für Angewandte Informatik (IAI)
Publikationstyp Zeitschriftenaufsatz
Jahr 2015
Sprache Englisch
Identifikator ISSN: 1932-6203
URN: urn:nbn:de:swb:90-508153
KITopen ID: 1000050815
HGF-Programm 47.01.02; LK 01
Erschienen in PLoS one
Band 10
Heft 10
Seiten Art.Nr.: e0137286
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
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