Free Radical Biology and Medicine | 2019
Inhibition of nuclear thioredoxin aggregation attenuates PM2.5‐induced NF‐&kgr;B activation and pro‐inflammatory responses
Abstract
ABSTRACT Exposure to fine particulate matter (PM2.5) can induce oxidative stress and proinflammatory cytokine production, which are central for the induction of PM2.5‐mediated adverse effects on public health. Nuclear factor kappa B (NF‐&kgr;B) signaling is essential for inflammation. The subcellular distribution of thioredoxin (Trx) is related to the activation of NF‐&kgr;B, but the mechanism involved is unclear. In the current study, we focused on the relationship between the antioxidant Trx and NF‐&kgr;B in human bronchial epithelial cells (BEAS‐2B) after PM2.5 exposure. We inhibited the nuclear translocation of Trx by cHCEU (4‐cyclohexyl‐[3‐(2‐chloroethyl)ureido]benzene) and subsequently increased the transcriptional activity of Nrf2 to upregulate the expression of Trx by t‐BHQ. Our data suggest that PM2.5 exposure induces the activation of NF‐&kgr;B and the expression of the downstream proinflammatory cytokines IL‐1, IL‐6, IL‐8 and TNF‐&agr; in BEAS‐2B cells. CHCEU alleviates inflammatory cytokines by blocking Trx nuclear translocation and inhibits the DNA binding activity of NF‐&kgr;B. T‐BHQ could promote the transcriptional activity of Nrf2 but failed to alleviate the production of inflammatory cytokines. Furthermore, the synergistic effect of t‐BHQ and cHCEU on alleviating PM2.5‐induced inflammation is more effective than the use of cHCEU alone. Our findings characterize the underlying molecular mechanisms of proinflammatory responses induced by PM2.5 and show that the nuclear translocation and accumulation of Trx in nuclei play important roles in PM2.5‐induced NF‐&kgr;B activation and proinflammatory responses. Graphical abstract Figure. No Caption available. HighlightsPM2.5 induces oxidative stress and pro‐inflammatory cytokine production in BEAS‐2B cell.PM2.5 promotes nuclear translocation of Trx and enhances DNA binding activity of NF‐&kgr;B.CHCEU alleviates the inflammatory cytokines by inhibiting Trx nuclear translocation.