Inhibition of nuclear thioredoxin aggregation attenuates PM_2.5-induced NF-κB activation and pro-inflammatory...

Exposure to fine particulate matter (PM_2.5) can induce oxidative stress and proinflammatory cytokine production, which are central for the induction of PM_2.5-mediated adverse effects on public health. Nuclear factor kappa B (NF-κB) signaling is essential for inflammation. The subcellular distribution of thioredoxin (Trx) is related to the activation of NF-κB, but the mechanism involved is unclear. In the current study, we focused on the relationship between the antioxidant Trx and NF-κB in human bronchial epithelial cells (BEAS-2B) after PM_2.5 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 PM_2.5 exposure induces the activation of NF-κB and the expression of the downstream proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-α in BEAS-2B cells. CHCEU alleviates inflammatory cytokines by blocking Trx nuclear translocation and inhibits the DNA binding activity of NF-κB. 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 PM_2.5-induced inflammation is more effective than the use of cHCEU alone. Our findings characterize the underlying molecular mechanisms of proinflammatory responses induced by PM_2.5 and show that the nuclear translocation and accumulation of Trx in nuclei play important roles in PM_2.5-induced NF-κB activation and proinflammatory responses.