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Published in: Respiratory Research 1/2018

Open Access 01-12-2018 | Research

Parthenolide attenuated bleomycin-induced pulmonary fibrosis via the NF-κB/Snail signaling pathway

Authors: Xiao-he Li, Ting Xiao, Jia-huan Yang, Yuan Qin, Jing-jing Gao, Hui-juan Liu, Hong-gang Zhou

Published in: Respiratory Research | Issue 1/2018

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Abstract

Background

Parthenolide (PTL) is a natural molecule isolated from Tanacetum parthenium that exhibits excellent anti-inflammatory and antitumor activities. Pulmonary fibrosis (PF), especially idiopathic pulmonary fibrosis (IPF), is a chronic lung disease that lacks a proven effective therapy. The present study evaluated the therapeutic effect of PTL on PF.

Methods

Serum-starved primary lung fibroblasts and HFL1 cells were treated with different doses of PTL, and cell viability and the migration rate were measured. Western blot analysis and a dual-luciferase assay were used to analyze the epithelial–mesenchymal transition (EMT)-related transcription factors influenced by PTL treatment in A549 cells and primary lung epithelial cells. Mice with bleomycin (BLM)-induced pulmonary fibrosis were treated with different doses of intragastric PTL, and pathological changes were evaluated using Hematoxylin-eosin (H&E) staining and immunohistochemical analysis.

Results

Our results demonstrated that PTL reduced the cell viability and migration rate of lung fibroblasts and inhibited the expression of EMT-related transcription factors in lung epithelial cells. In vivo studies demonstrated that PTL attenuated BLM-induced pulmonary fibrosis and improved the body weight and pathological changes of BLM-treated mice. We further demonstrated that PTL attenuated BLM-induced PF primarily via inhibition of the NF-κB/Snail signaling pathway.

Conclusion

These findings suggest that PTL inhibits EMT and attenuates BLM-induced PF via the NF-κB/Snail signaling pathway. PTL is a worthwhile candidate compound for pulmonary fibrosis therapy.
Literature
1.
go back to reference Foster MW, et al. Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis. J Proteome Res. 2015;14:1238–49.CrossRefPubMed Foster MW, et al. Quantitative proteomics of bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis. J Proteome Res. 2015;14:1238–49.CrossRefPubMed
2.
go back to reference Kim KK, et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci U S A. 2006;103(35):13180.CrossRefPubMedPubMedCentral Kim KK, et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci U S A. 2006;103(35):13180.CrossRefPubMedPubMedCentral
3.
go back to reference Azuma A, et al. Double-blind, placebo-controlled trial of Pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2005;171:1040–7.CrossRefPubMed Azuma A, et al. Double-blind, placebo-controlled trial of Pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2005;171:1040–7.CrossRefPubMed
4.
go back to reference Ikeda S, et al. Hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis: a single-center experience. Respir Investig. 2017;55(1):51.CrossRefPubMed Ikeda S, et al. Hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis: a single-center experience. Respir Investig. 2017;55(1):51.CrossRefPubMed
5.
go back to reference Shi K, et al. Dexamethasone attenuates bleomycin-induced lung fibrosis in mice through TGF-β, Smad3 and JAK-STAT pathway. Int J Clin Exp Med. 2014;7(9):2645.PubMedPubMedCentral Shi K, et al. Dexamethasone attenuates bleomycin-induced lung fibrosis in mice through TGF-β, Smad3 and JAK-STAT pathway. Int J Clin Exp Med. 2014;7(9):2645.PubMedPubMedCentral
6.
go back to reference Dik WA, et al. Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity. Eur Respir J. 2003;21(5):842–7.CrossRefPubMed Dik WA, et al. Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity. Eur Respir J. 2003;21(5):842–7.CrossRefPubMed
7.
go back to reference Chen F, et al. Short courses of low dose dexamethasone delay bleomycin-induced lung fibrosis in rats. Eur J Phamacol. 2006;536(3):287–95.CrossRef Chen F, et al. Short courses of low dose dexamethasone delay bleomycin-induced lung fibrosis in rats. Eur J Phamacol. 2006;536(3):287–95.CrossRef
8.
go back to reference Han Y, et al. Comparison of a loading dose of dexmedetomidine combined with propofol or sevoflurane for hemodynamic changes during anesthesia maintenance: a prospective, randomized, double-blind, controlled clinical trial. BMC Anesthesiol. 2018;18:12.CrossRefPubMedPubMedCentral Han Y, et al. Comparison of a loading dose of dexmedetomidine combined with propofol or sevoflurane for hemodynamic changes during anesthesia maintenance: a prospective, randomized, double-blind, controlled clinical trial. BMC Anesthesiol. 2018;18:12.CrossRefPubMedPubMedCentral
9.
go back to reference Willis BC, et al. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol. 2005;166(5):1321.CrossRefPubMedPubMedCentral Willis BC, et al. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol. 2005;166(5):1321.CrossRefPubMedPubMedCentral
10.
go back to reference Zank DC, et al. Idiopathic pulmonary fibrosis: aging, mitochondrial dysfunction and celluar bioenergetics. Front Med. 2018;5(10):1–9. Zank DC, et al. Idiopathic pulmonary fibrosis: aging, mitochondrial dysfunction and celluar bioenergetics. Front Med. 2018;5(10):1–9.
11.
go back to reference Chen T, et al. Epithelial–mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway. Toxicol Lett. 2014;226(2):150–62.CrossRefPubMed Chen T, et al. Epithelial–mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway. Toxicol Lett. 2014;226(2):150–62.CrossRefPubMed
12.
go back to reference Ghantous A, et al. Parthenolide: from plant shoots to cancer roots. Drug Discov Today. 2013;18(17–18):894–905.CrossRefPubMed Ghantous A, et al. Parthenolide: from plant shoots to cancer roots. Drug Discov Today. 2013;18(17–18):894–905.CrossRefPubMed
13.
go back to reference Hehner SP, et al. The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-kappa B by targeting the I kappa B kinase complex. J Immunol. 1999;163:5617–23.PubMed Hehner SP, et al. The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-kappa B by targeting the I kappa B kinase complex. J Immunol. 1999;163:5617–23.PubMed
14.
go back to reference Jiang D, et al. Regulation of lung injury and repair by toll-like receptors and hyaluronan. Nat Med. 2005;11:1173–9.CrossRefPubMed Jiang D, et al. Regulation of lung injury and repair by toll-like receptors and hyaluronan. Nat Med. 2005;11:1173–9.CrossRefPubMed
16.
go back to reference Zhang S, et al. Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms. Curr Med Chem Anticancer Agents. 2005;5:239–49.CrossRefPubMed Zhang S, et al. Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms. Curr Med Chem Anticancer Agents. 2005;5:239–49.CrossRefPubMed
17.
go back to reference Kwok BH, et al. The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 2001;8:759–66.CrossRefPubMed Kwok BH, et al. The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 2001;8:759–66.CrossRefPubMed
19.
go back to reference Wiedhopf RM, et al. Tumor inhibitory agent from Magnolia grandiflora (Magnoliaceae). I. Parthenolide. J Pharm Sci. 1973;62:345.CrossRefPubMed Wiedhopf RM, et al. Tumor inhibitory agent from Magnolia grandiflora (Magnoliaceae). I. Parthenolide. J Pharm Sci. 1973;62:345.CrossRefPubMed
20.
go back to reference Jia QQ, et al. Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-κB activation and MCP-1 and TGF-β1 expression in rat mesangial cells. Molecules. 2013;18(10):13061–77.CrossRefPubMed Jia QQ, et al. Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-κB activation and MCP-1 and TGF-β1 expression in rat mesangial cells. Molecules. 2013;18(10):13061–77.CrossRefPubMed
21.
go back to reference Kim HY, et al. Balsalazide potentiates Parthenolide-mediated inhibition of nuclear factor-κB signaling in HCT116 human colorectal Cancer cells. Intest Res. 2015;13(3):233–41.CrossRefPubMedPubMedCentral Kim HY, et al. Balsalazide potentiates Parthenolide-mediated inhibition of nuclear factor-κB signaling in HCT116 human colorectal Cancer cells. Intest Res. 2015;13(3):233–41.CrossRefPubMedPubMedCentral
22.
go back to reference Driscoll KE, Maurer JK. Cytokine and growth factor release by alveolar macrophages: potential biomarkers of pulmonary toxicity. Toxicol Pathol. 1991;19(1):398–405.CrossRefPubMed Driscoll KE, Maurer JK. Cytokine and growth factor release by alveolar macrophages: potential biomarkers of pulmonary toxicity. Toxicol Pathol. 1991;19(1):398–405.CrossRefPubMed
23.
go back to reference Savici D, et al. Silica increases tumor necrosis factor (TNF) production, in part, by upregulating the TNF promoter. Exp Lung Res. 1994;102(6):613–25.CrossRef Savici D, et al. Silica increases tumor necrosis factor (TNF) production, in part, by upregulating the TNF promoter. Exp Lung Res. 1994;102(6):613–25.CrossRef
24.
go back to reference Bartram U, Speer CP. The role of transforming growth factor beta in lung development and disease. Chest. 2004;125(2):754.CrossRefPubMed Bartram U, Speer CP. The role of transforming growth factor beta in lung development and disease. Chest. 2004;125(2):754.CrossRefPubMed
25.
go back to reference Doyle SL, et al. Nuclear factor κB2 p52 protein has a role in antiviral immunity through IκB kinase ϵ-dependent induction of Sp1 protein and interleukin 15. J Biol Chem. 2013;288(35):25066.CrossRefPubMedPubMedCentral Doyle SL, et al. Nuclear factor κB2 p52 protein has a role in antiviral immunity through IκB kinase ϵ-dependent induction of Sp1 protein and interleukin 15. J Biol Chem. 2013;288(35):25066.CrossRefPubMedPubMedCentral
26.
go back to reference Sivakumar P, et al. Into the matrix: targeting fibroblasts in pulmonary fibrosis. Curr Opin Pulm Med. 2012;18(5):462–9.CrossRefPubMed Sivakumar P, et al. Into the matrix: targeting fibroblasts in pulmonary fibrosis. Curr Opin Pulm Med. 2012;18(5):462–9.CrossRefPubMed
27.
go back to reference Piek E, Heldin C, Dijke PT. Specificity, diversity, and regulation in TGF-β superfamily signaling. FASEB J. 1999;13(15):2105.CrossRefPubMed Piek E, Heldin C, Dijke PT. Specificity, diversity, and regulation in TGF-β superfamily signaling. FASEB J. 1999;13(15):2105.CrossRefPubMed
28.
go back to reference Nakamuta M, et al. Effects of fibril- or fixed-collagen on matrix metalloproteinase-1and tissue inhibitor of matrix metalloproteinase-1 production in the human hepatocyte cell line HLE. World J Gastroenterol. 2005;11(15):2264–8.CrossRefPubMedPubMedCentral Nakamuta M, et al. Effects of fibril- or fixed-collagen on matrix metalloproteinase-1and tissue inhibitor of matrix metalloproteinase-1 production in the human hepatocyte cell line HLE. World J Gastroenterol. 2005;11(15):2264–8.CrossRefPubMedPubMedCentral
29.
go back to reference Pardo A, et al. Role of matrix metalloproteinases in the pathogenesis of idiopathic pulmonary fibrosis. Respir Res. 2016;17(1):1–10.CrossRef Pardo A, et al. Role of matrix metalloproteinases in the pathogenesis of idiopathic pulmonary fibrosis. Respir Res. 2016;17(1):1–10.CrossRef
30.
go back to reference Darby IA, et al. The myofibroblast, a key cell in normal and pathological tissue repair. Cell Mol Life Sci. 2016;73(6):1145–57.CrossRefPubMed Darby IA, et al. The myofibroblast, a key cell in normal and pathological tissue repair. Cell Mol Life Sci. 2016;73(6):1145–57.CrossRefPubMed
31.
go back to reference Corvol H, et al. Lung alveolar epithelium and interstitial lung disease. Int J Biochem Cell Biol. 2009;41(8–9):1643.CrossRefPubMed Corvol H, et al. Lung alveolar epithelium and interstitial lung disease. Int J Biochem Cell Biol. 2009;41(8–9):1643.CrossRefPubMed
33.
go back to reference Horowitz JC, Thannickal VJ. Epithelial-mesenchymal interactions in pulmonary fibrosis. Semin Respir Crit Care Med. 2006;27(6):600. Horowitz JC, Thannickal VJ. Epithelial-mesenchymal interactions in pulmonary fibrosis. Semin Respir Crit Care Med. 2006;27(6):600.
34.
go back to reference Ohbayashi M, et al. Involvement of epithelial-mesenchymal transition in methotrexate-induced pulmonary fibrosis. J Toxicol Sci. 2014;39(2):319–30.CrossRefPubMed Ohbayashi M, et al. Involvement of epithelial-mesenchymal transition in methotrexate-induced pulmonary fibrosis. J Toxicol Sci. 2014;39(2):319–30.CrossRefPubMed
Metadata
Title
Parthenolide attenuated bleomycin-induced pulmonary fibrosis via the NF-κB/Snail signaling pathway
Authors
Xiao-he Li
Ting Xiao
Jia-huan Yang
Yuan Qin
Jing-jing Gao
Hui-juan Liu
Hong-gang Zhou
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2018
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-018-0806-z

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