文摘
Tumor necrosis factor x3b1; (TNFx3b1;) is a cytokine inducing inflammatory responses. It has been reported that ethyl pyruvate has anti-inflammatory actions through inhibition of the transcription mediated by nuclear factor-kappa B (NF-x3ba;B). By reporter gene assay, we first confirmed that TNFx3b1; activated the NF-x3ba;B pathway in cultured alveolar epithelial cells, A549 cells. This activation was strongly inhibited by ethyl pyruvate in a concentration-dependent manner. Treatment of the cells with TNFx3b1;-induced phosphorylation and degradation of Ix3ba;Bx3b1; within 15 min. The level of Ix3ba;Bx3b1; protein was increased from 30 min, suggesting an increase in the NF-x3ba;B-mediated transcription of Ix3ba;Bx3b1;. Ethyl pyruvate did not affect the changes in Ix3ba;Bx3b1; within 15 min, but strongly inhibited the increase in the Ix3ba;Bx3b1; protein level from 30 min. An immunoblot analysis revealed that ethyl pyruvate inhibited the nuclear translocation of RelA from 5 min of the treatment with TNFx3b1;. These results strongly suggested that ethyl pyruvate inhibited the NF-x3ba;B pathway through inhibition of the nuclear translocation of RelA. Ethyl pyruvate may be a good therapeutic drug for inflammation in which activation of the NF-x3ba;B pathway is involved.