Fig. 4.

Role of thioredoxin in SOCS1-induced suppression of LPS response for ROS generation and inflammasome activation associated with IL-1β production. Flag-SOCS1 THP1 cells were further transfected with sh/shTrx1 and the intracellular ROS levels were analyzed following LPS stimulation (A). The role of Trx1 and SOCS1 in LPS-induced, ROS-promoted inflammasome activation was analyzed. Cells were stimulated with LPS for 4 h and treated with nigericin (NIG) as indicated. Activation of ASC, NLRP3 and caspase-1 was then analyzed by immunoblotting and the secreted IL-1β protein was measured by ELISA (B-E). The proposed model represents the inhibitory mechanism of SOCS1 in TLR4 signaling leading to inflammatory cytokine production via downregulation of ROS (F). The details are described in Supplementary Materials.