Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity

Aim： Daidzein （4＇,7-dihydroxyisoflavone） is an isoflavone exiting in many herbs that has shown anti-inflammation activity. The aim of this study was to investigate the mechanism underlying its anti-inflammatory action in murine lung epithelial cells. Methods： C57BL/6 mice were intranasally exposed t...

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Published in:	Acta pharmacologica Sinica 2014-04, Vol.35 (4), p.496-503
Main Authors:	Li, Hai-yan, Pan, Lang, Ke, Yue-shuang, Batnasan, Enkhzaya, Jin, Xiang-qun, Liu, Zhong-ying, Ba, Xue-qing
Format:	Article
Language:	eng
Subjects:	Animals Anti-Inflammatory Agents - pharmacology Cell Line Chemokine CXCL2 - genetics Chemokine CXCL2 - metabolism Disease Models, Animal Dose-Response Relationship, Drug Down-Regulation Enzyme Inhibitors - pharmacology Epithelial Cells - drug effects Epithelial Cells - immunology Epithelial Cells - metabolism Genes, Reporter Isoflavones - pharmacology Lung - drug effects Lung - immunology Lung - metabolism Male Mice, Inbred C57BL Original Pneumonia - chemically induced Pneumonia - immunology Pneumonia - metabolism Pneumonia - prevention & control Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerase Inhibitors Poly(ADP-ribose) Polymerases - genetics Poly(ADP-ribose) Polymerases - metabolism RNA, Messenger - metabolism Signal Transduction - drug effects Time Factors TNF-α Transcription Factor RelA - genetics Transcription Factor RelA - metabolism Transcription, Genetic - drug effects Transfection Tumor Necrosis Factor-alpha 大豆苷元小鼠活性抑制炎症肺上皮细胞趋化因子转录活性
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Summary:	Aim： Daidzein （4＇,7-dihydroxyisoflavone） is an isoflavone exiting in many herbs that has shown anti-inflammation activity. The aim of this study was to investigate the mechanism underlying its anti-inflammatory action in murine lung epithelial cells. Methods： C57BL/6 mice were intranasally exposed to TNF-α to induce lung inflammation. The mice were injected with daidzein （400 mg/kg, ip） before TNF-α challenge, and sacrificed 12 h after TNF-α challenge, and lung tissues were collected for analyisis. In in vitro studies, murine MLE-12 epithelial cells were treated with TNF-α （20 ng/mL）. The expression of pro-inflammatory chemokine Cxcl2 mRNA and NF-κB transcriptional activity were examined using real-time PCR and a dual reporter assay. Protein poly-adenosine diphosphate-ribosylation （PARylation） was detecyed using Western blotting and immunoprecipitation assays. Results： Pretreatment of the mice with daidzein markedly attenuated TNF-α-induced lung inflammation, and inhibited Cxcl2 expression in lung tissues. Furthermore, daidzein （10 μmol/L） prevented TNF-α-induced increases in Cxcl2 expression and activity and NF-κB transcriptional activity, and markedly inhibited TNF-α-induced protein PARylation in MLE-12 cells in vitro. In MLE-12 cells co-transfected with the PARP-1 expression plasmid and NF-κB-luc （or Cxcl2-luc） reporter plasmid, TNF-α markedly increased NF-κB （or Cxcl2） activation, which were significantly attenuated in the presence of daidzein （or the protein PARylation inhibitor PJ 34）. PARP-1 activity assay showed that daidzein （10 μmol/L） reduced the activity of PARP-1 by ~75%. Conclusion： The anti-inflammatory action of daidzein in murine lung epithelial cells seems to be mediated via a direct interaction with PARP-1, which inhibits RelA/p65 protein PARylation required for the transcriptional modulation of pro-inflammatory chemokines such as Cxcl2.
ISSN:	1671-4083 1745-7254