Defect in mevalonate pathway induces pyroptosis in Raw 264.7 murine monocytes

Annalisa Marcuzzi, Elisa Piscianz, Martina Girardelli, Sergio Crovella, Alessandra Pontillo

Research output: Contribution to journalArticle

Abstract

The inhibition of mevalonate pathway by the aminobisphosphonate alendronate (ALD) has been previously associated with an augmented lipopolysaccharide- induced interleukin-1beta (IL-1β) secretion in monocytes, as demonstrated in an auto-inflammatory disease known as mevalonate kinase deficiency (MKD). In this study we investigated the effect of ALD + LPS on monocyte cell line (Raw 264.7) death. ALD strongly augmented LPS-induced programmed cell death (PCD) as well as IL-1β secretion in Raw murine monocytes, whereas necrosis was rather unaffected. ALD + LPS induced caspase-3 activation. Inhibition of IL-1β stimulation partially restored cell viability. These findings suggest that the inhibition of mevalonate pathway, together with a bacterial stimulus, induce a PCD partly sustained by the caspase-3-related apoptosis and partly by caspase-1-associated pyroptosis. The involvement of pyroptosis is a novel hit in our cell model and opens discussions about its role in inflammatory cells with chemical or genetic inhibition of mevalonate pathway.

Original languageEnglish
Pages (from-to)882-888
Number of pages7
JournalApoptosis
Volume16
Issue number9
DOIs
Publication statusPublished - Sep 2011

Keywords

  • Apoptosis
  • Caspase
  • Mevalonate
  • Pyroptosis

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Biochemistry, medical
  • Cancer Research
  • Pharmaceutical Science
  • Pharmacology

Fingerprint Dive into the research topics of 'Defect in mevalonate pathway induces pyroptosis in Raw 264.7 murine monocytes'. Together they form a unique fingerprint.

  • Cite this