A Zebrafish Drug-Repurposing Screen Reveals sGC-Dependent and sGC-Independent Pro-Inflammatory Activities of Nitric Oxide.
PLoS One
; 10(10): e0137286, 2015.
Article
em En
| MEDLINE
| ID: mdl-26444552
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Citoplasmáticos e Nucleares
/
Mediadores da Inflamação
/
Reposicionamento de Medicamentos
/
Guanilato Ciclase
/
Inflamação
/
Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha