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J Immunol. 2009 Jul 15;183(2):1456-62. doi: 10.4049/jimmunol.0900578. Epub 2009 Jun 26.

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

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Cell Biology Unit, National Cancer Research Institute, Genova, Italy.


In this study, we show that IL-1beta 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-1beta. ROS production and antioxidant response are both required, because either inhibitors of NADPH oxidase and of thioredoxin reductase impair IL-1beta secretion. These inhibitors also hinder cysteine release and consequently prevent reduction of the extracellular medium: addition of exogenous reducing agents restores IL-1beta secretion. Not only silencing of thioredoxin, but also of the ROS scavenger superoxide dismutase 1 results in inhibition of IL-1beta secretion. Thus, PAMP-induced ROS trigger an antioxidant response involving intracellular redox enzymes and release of cysteine, ultimately required for IL-1beta processing and secretion.

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