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Identification and validation of uterine stimulant methylergometrine as a potential inhibitor of caspase-1 activation

Authors :
Mónica Sancho
Mar Orzáez
Vanessa García-Bayarri
Guillermo García-Laínez
Source :
Apoptosis, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe, instname, APOPTOSIS, r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF), r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF), Centro de Investigación Principe Felipe (CIPF)
Publication Year :
2017
Publisher :
Kluwer Academic Publishers, 2017.

Abstract

Inflammasomes are intracellular multiprotein complexes of the innate immune system. Upon an inflammatory insult, such as infection or intracellular damage, a nucleotide-binding oligomerization domain-like receptor (NLR) sensor protein and the adaptor protein ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain) are assembled to activate protease procaspase-1. This protease processes pro-IL-1β and pro-IL-18 cytokines, which are released to induce the inflammatory response. De-regulation of inflammasome contributes to the progression of several diseases, such as Alzheimer’s disease, diabetes, cancer, inflammatory and autoimmune disorders. We herein describe the identification of methylergometrine (MEM), a drug currently used as a smooth muscle constrictor during postpartum hemorrhage, as an inhibitor of the inflammasome complex in ASC-mediated procaspase-1 activation screening. MEM inhibits the activation of the nucleotide-binding oligomerization domain-like receptor protein 1 (NLRP1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes in cellular models upon different pro-inflammatory stimuli. Our results suggest that MEM has the potential to reposition in the treatment of inflammatory diseases with the advantages of established safety and clinical data. Electronic supplementary material The online version of this article (doi:10.1007/s10495-017-1405-z) contains supplementary material, which is available to authorized users.

Details

ISSN :
13608185
Database :
OpenAIRE
Journal :
Apoptosis, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe, instname, APOPTOSIS, r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF), r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF), Centro de Investigación Principe Felipe (CIPF)
Accession number :
edsair.doi.dedup.....406835934b31bb28676efc0b2bf20ccc