Inhibition by ethyl pyruvate of the nuclear translocation of nuclear factor-kappaB in cultured lung epithelial cells.

Abstract

Tumor necrosis factor alpha (TNFalpha) 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-kappaB). By reporter gene assay, we first confirmed that TNFalpha activated the NF-kappaB 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 TNFalpha-induced phosphorylation and degradation of IkappaBalpha within 15 min. The level of IkappaBalpha protein was increased from 30 min, suggesting an increase in the NF-kappaB-mediated transcription of IkappaBalpha. Ethyl pyruvate did not affect the changes in IkappaBalpha within 15 min, but strongly inhibited the increase in the IkappaBalpha 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 TNFalpha. These results strongly suggested that ethyl pyruvate inhibited the NF-kappaB 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-kappaB pathway is involved.

• Authors: Ayako Mizutani, Noriko Maeda, Seikichi Toku, Yoichiro Isohama, Kazuhiro Sugahara, Hideyuki Yamamoto
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 23 Issue 4 Pg. 308-15 (Aug 2010) ISSN: 1522-9629 [Electronic] England
• PMID: 20302967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Chemical References

• I-kappa B Proteins
• NF-kappa B
• NFKBIA protein, human
• Pyruvates
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• ethyl pyruvate
• NF-KappaB Inhibitor alpha

Topics

• Cell Line
• Cell Nucleus (metabolism)
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, metabolism)
• Genes, Reporter
• Humans
• I-kappa B Proteins (metabolism)
• Immunoblotting
• NF-KappaB Inhibitor alpha
• NF-kappa B (drug effects, metabolism)
• Phosphorylation
• Protein Transport
• Pulmonary Alveoli (cytology, drug effects, metabolism)
• Pyruvates (administration & dosage, pharmacology)
• Time Factors
• Transcription Factor RelA (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)