Figure 5. Diabetes increases neutrophil extracellular traps (NETs), priming macrophages for inflammation.
Increased ROS increase transcription and activation of peptidylarginine deiminase 4 (PAD4), the enzyme which initiates formation and release of NETs by citrullination of histones. Released NETs prime macrophages to produce pro-IL-1β, which is cleaved to mature pro-inflammatory IL-1β by caspase 1 secreted by macrophages in response to NLRP3 inflammasome activation. Cit, citrullination; αH4R, αhistone 4 Arginine; αH4cit, αhistone 4 with arginine residues converted to citrulline.