PUBLICATION
A Zebrafish Drug-Repurposing Screen Reveals sGC-Dependent and sGC-Independent Pro-Inflammatory Activities of Nitric Oxide
- Authors
- Wittmann, C., Reischl, M., Shah, A.H., Kronfuss, E., Mikut, R., Liebel, U., Grabher, C.
- ID
- ZDB-PUB-151008-3
- Date
- 2015
- 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
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/pharmacology
- Cells, Cultured
- Copper Sulfate/toxicity
- Drug Repositioning/methods*
- Free Radical Scavengers/pharmacology
- Gene Knockdown Techniques
- Guanylate Cyclase/metabolism*
- Inflammation/drug therapy*
- Inflammation/genetics
- Inflammation Mediators/pharmacology*
- Larva/drug effects
- Leukocytes/immunology
- Morpholinos/genetics
- Mucous Membrane/drug effects
- Mucous Membrane/injuries
- Nitric Oxide/pharmacology*
- Nitric Oxide Synthase Type I/genetics
- Nitric Oxide Synthase Type II/genetics
- Peripheral Nervous System/drug effects
- Receptors, Cytoplasmic and Nuclear/metabolism*
- Soluble Guanylyl Cyclase
- Zebrafish
- PubMed
- 26444552 Full text @ PLoS One
Citation
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.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping