Reactive Oxygen Species in Inflammasome Activation
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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.