Damage control: management of cellular stress by the NLRP3 inflammasome

Abstract

The NLRP3 inflammasome plays a critical role in regulating inflammatory and cell death pathways in response to a diverse array of stimuli. Activation of the NLRP3 inflammasome results in activation of the cysteine protease caspase-1 and the subsequent processing and secretion of the proinflammatory cytokines IL-1β and IL-18. In this issue of the European Journal of Immunology, Licandro et al. [Eur. J. Immunol. 2013. 43, 2126-2137] show that the NLRP3 inflammasome contributes to oxidative DNA damage. In addition, activation of the NLRP3 inflammasome modulates a number of pathways involved in DNA damage repair, cell cycle, and apoptosis, suggesting a novel role for the NLRP3 inflammasome in DNA damage responses following cellular stress.

Keywords: Caspase-1; DC; Genotoxic stress; NLRP3 inflammasome.

Figure 1

The NLRP3 inflammasome regulates the DNA damage response pathway. In the model proposed by Licandro et al.[14] oxidative DNA damage is induced in dendritic cells by monosodium urate (MSU) or high dose γ-radiation. Concurrent NLRP3 inflammasome activation results in (1) stabilization of p53 resulting in increased cell death; (2) a downregulation of pro-survival genes Xiap and Birc3; (3) a suppression of double-strand and base-excision DNA repair pathways.