|ZFIN ID: ZDB-PUB-151008-3|
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.
|Source:||PLoS One 10: e0137286 (Journal)|
|Registered Authors:||Grabher, Clemens, Liebel, Urban, Mikut, Ralf, Shah, Asmi, Wittmann, Christine|
|Keywords:||Inflammation, Nitric oxide, Zebrafish, Larvae, S-nitrosylation, White blood cells, Library screening, Peripheral nervous system|
|PubMed:||26444552 Full text @ PLoS One|
Wittmann, C., Reischl, M., Shah, A.H., Kronfuss, E., Mikut, R., Liebel, U., Grabher, C. (2015) A Zebrafish Drug-Repurposing Screen Reveals sGC-Dependent and sGC-Independent Pro-Inflammatory Activities of Nitric Oxide. PLoS One. 10:e0137286.
ABSTRACTTissue 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.