Reactive oxygen species at the crossroads of inflammasome and inflammation

Citations Over TimeTop 1% of 2014 papers

Abstract

Inflammasomes form a crucial part of the innate immune system. These are multi-protein oligomer platforms that are composed of intracellular sensors which are coupled with caspase and interleukin activating systems. Nod-like receptor protein (NLRP) 3, and 6 and NLRC4 and AIM2 are the prominent members of the inflammasome family. Inflammasome activation leads to pyroptosis, a process of programmed cell death distinct from apoptosis through activation of Caspase and further downstream targets such as IL-1β and IL-18 leading to activation of inflammatory cascade. Reactive oxygen species (ROS) serves as important inflammasome activating signals. ROS activates inflammasome through mitogen-activated protein kinases (MAPK) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Dysregulation of inflammasome plays a significant role in various pathological processes. Viral infections such as Dengue and Respiratory syncytial virus activate inflammasomes. Crystal compounds in silicosis and gout also activate ROS. In diabetes, inhibition of autophagy with resultant accumulation of dysfunctional mitochondria leads to enhanced ROS production activating inflammasomes. Activation of inflammasomes can be dampened by antioxidants such as SIRT-1. Inflammasome and related cascade could serve as future therapeutic targets for various pathological conditions.

Related Papers

• → Recent advances in inflammasome biology(2017)328 cited
• → Crystal Structure of NALP3 Protein Pyrin Domain (PYD) and Its Implications in Inflammasome Assembly(2011)192 cited
• → Quercetin Inhibits Inflammasome Activation by Interfering with ASC Oligomerization and Prevents Interleukin-1 Mediated Mouse Vasculitis(2017)96 cited
• → Pyrin Domain (PYD)-containing Inflammasome in Innate Immunity(2011)19 cited
• → LRR-protein RNH1 dampens the inflammasome activation and is associated with COVID-19 severity(2022)15 cited