Reactive Oxygen Species in Inflammasome Activation

Abstract

The fundamental role of the innate immune system is to form the first barrier in bacterial and viral defence. It is based upon the recognition of pathogenic-associated molecular patterns (PAMPs) by germ-encoded pattern recognition receptors (PRRs).Intracellular PAMP recognition is accomplished by cytosolic nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs).NLR activation leads to the activation of the inflammasome, a multiprotein platform which activates pro-caspase-1. Caspase-1 proteolytically activates IL-1beta. Reactive oxygen species have been linked to inflammasome activation and IL-1beta secretion. The model reviewed in this thesis is based up on ATP-P2x7-receptor activation-mediated NADPH-oxidase induced ROS production. This activates ERK1/2 and consequently the NLRP3-Inflammasome. However, the exact mechanisms of signaling downstream of ERK1/2 to caspase-1 are still unknown.