Nrf2 inhibits NLRP3 inflammasome activation in cerebral injury
The nod-like receptor protein (NLRP3) inflammasome includes a important function in inflammation harm in irreparable injury, and also the activation of the inflammasome is closely linked to the interaction with thioredoxin interacting protein (TXNIP), which dissociates in the thioredoxin1 (Trx1)/TXNIP complicated under oxidative stress. On the other hand, the negative regulator of NLRP3 inflammasome activation hasn’t been completely researched. Nuclear factor erythroid 2-related factor 2 (Nrf2) happens on a important role in the antioxidant pressure system, which controls the driven genes of antioxidant response element (ARE). Activate Nrf2 could inhibit the regeneration of NLRP3 inflammasome in severe liver injury and acute lupus nephritis. We planned to explore the protective impact of Nrf2 in inhibiting the NLPR3 inflammasome formula through the Trx1/TXNIP complicated in cerebral ischemia reperfusion (cerebral I/R) injury. Middle cerebral artery occlusion/reperfusion (MCAO/R) version was used to mimic ischemic insult. Nrf2 was triggered by tert-butylhydroquinone (tBHQ) intraperitoneally (i.p.) injection (16.7mg/kg), Nrf2,Trx1 and NLRP3 siRNAs were implanted to the abandoned paracele (12μl per rat), protein and mRNA levels were evaluated by Western blot, qRT-PCR. ELISA was used for IL-1β and IL-18 actions dimensions. Following upregulating Nrf2, the saying of TXNIP at cytoplasm, NLRP3 inflammasome, and downstream factors caspase-1, IL-18, and IL-1β were considerably diminished, and Nrf2 knockdown yielded the opposite effects. Trx1 knockdown created the exact same impact of Nrf2 inhibition along with the protective impact of Nrf2 was largely abolished. Our results implied that Nrf2 acted as a protective ruler contrary to NLRP3 inflammasome activation by regulating the Trx1/TXNIP complicated, which may potentially reflect an innovative insight to treating ischemia and reperfusion injury.Details: Inflammation; Nod-like receptor protein inflammasome; Nuclear factor erythroid 2-related variable two; Thioredoxin interacting protein; Thioredoxin1.