Pathogen-induced interleukin-1β processing and secretion is regulated by a biphasic redox response

Sara Tassi, Sonia Carta, Roberta Vené, Laura Delfino, Maria Rosa Ciriolo, Anna Rubartelli

Research output: Contribution to journalArticlepeer-review

Abstract

In this study, we show that IL-1β processing and secretion induced by pathogen-associated molecular pattern (PAMP) molecules in human monocytes is regulated by a biphasic redox event including a prompt oxidative stress and a delayed antioxidant response. Namely, PAMPs induce an early generation of reactive oxygen species (ROS) followed by increase of intracellular thioredoxin and release of reduced cysteine: this antioxidant phase is paralleled by secretion of mature IL-1β. ROS production and antioxidant response are both required, because either inhibitors of NADPH oxidase and of thioredoxin reductase impair IL-1β secretion. These inhibitors also hinder cysteine release and consequently prevent reduction of the extracellular medium: addition of exogenous reducing agents restores IL-1β secretion. Not only silencing of thioredoxin, but also of the ROS scavenger superoxide dismutase 1 results in inhibition of IL-1β secretion. Thus, PAMP-induced ROS trigger an antioxidant response involving intracellular redox enzymes and release of cysteine, ultimately required for IL-1β processing and secretion.

Original languageEnglish
Pages (from-to)1456-1462
Number of pages7
JournalJournal of Immunology
Volume183
Issue number2
DOIs
Publication statusPublished - Jul 15 2009

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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