Figure 10. Proposed model illustrating how melatonin protects smoking-related vascular inflammatory injury through Nrf2/ROS/NLRP3 axis. ROS induced by smoking increased NLRP3 transcription and subsequent inflammasome activation, which promoted secretion of mature IL-1β and IL-18. ROS also stimulated the nuclear translocation of Nrf2 as a negative feedback. Melatonin induces the nuclear translocation of Nrf2, downstream expression, and elimination of intracellular ROS, resulting in a decrease in the transcription level of NLRP3 and downstream inflammasome activation.