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Therapeutic Effects of Resveratrol in a Mouse Model of LPS and Cigarette Smoke-Induced COPD

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Abstract

This study was designed to examine whether resveratrol exerts the protective effects on LPS and cigarette smoke (LC)-induced COPD in a murine model. In lung histopathological studies, H&E, Masson’s trichrome, and AB-PAS staining were performed. The cytokines (IL-6, IL-17, TGF-β, and TNF-α) and inflammatory cells in BALF were determined. The Beclin1 level in the lungs of mouse was analyzed. Compared with the LC-induced mouse, the level of inflammatory cytokines (IL-17, IL-6, TNF-α, and TGF-β) of the BALF in the resveratrol + cigarette smoke-treated mouse had obviously decreased. Histological examination of the lung tissue revealed that the resveratrol treatment attenuated the fibrotic response and mucus hypersecretion. In addition, resveratrol inhibited the expression of the Beclin1 protein in mouse lungs. The presented findings collectively suggest that resveratrol has a therapeutic effect on mouse LC-induced COPD, and its mechanism of action might be related to reducing the production of the Beclin1 protein.

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Abbreviations

COPD:

Chronic obstructive pulmonary disease

DEX:

Dexamethasone

BALF:

Bronchoalveolar lavage fluid

PBS:

Phosphate buffered physiological saline

RES:

Resveratrol

LC:

LPS + cigarette smoke

References

  1. Wollin, L., and M.P. Pieper. 2010. Tiotropium bromide exerts anti-inflammatory activity in a cigarette smoke mouse model of COPD. Pulmonary Pharmacology & Therapeutics 23(2010): 345–354.

    Article  CAS  Google Scholar 

  2. Tamini, A., D. Serdarevic, and N.A. Hanania. 2012. The effects of cigarette smoke on airway inflammation in asthma and COPD: therapeutic implications. Respiratory Medicine 106(2012): 319–328.

    Article  Google Scholar 

  3. Busse, P.J., T.F. Zhang, K. Srivastava, B.P. Lin, B. Schofield, S.C. Sealfon, and X.M. Li. 2005. Chronic exposure to TNF-alpha increases airway mucus gene expression in vivo. Journal of Allergy and Clinical Immunology 116(6): 1256–1263.

    Article  CAS  PubMed  Google Scholar 

  4. Numasaki, M., Y. Tomioka, H. Takahashi, and H. Sasaki. 2004. IL-17 and IL-17F modulate GM-CSF production by lung microvascular endothelial cells stimulated with IL-1beta and/or TNF-alpha. Immunology Letters 95(2): 175–184.

    Article  CAS  PubMed  Google Scholar 

  5. Friedrichs, B., U. Neumann, J. Schuller, and M.J. Peck. 2014. Cigarette-smoke-induced priming of neutrophils from smokers and non-smokers for increased oxidative burst response is mediated by TNF-alpha. Toxicology In Vitro : An International Journal Published in Association with BIBRA 28(7): 1249–1258.

    Article  CAS  Google Scholar 

  6. Kohri, K., R.F. Ueki, and A.A. Nadel. 2002. Neutrophil elastase induces mucin production by ligand-dependent pidermal growth factor receptor activation. American Journal of Physiology Lung Cellular and Molecular Physiology 283(3): 531–540.

    Article  Google Scholar 

  7. Ryter, S.W., S.-J. Lee, and A.M. Choi. 2010. Autophagy in cigarette smoke-induced chronic obstructive pulmonary disease. Expert Review of Respiratory Medicine 4(5): 573–584.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wang, X., Y. Wang, X. Zhao, R. Andersson, Z. Song, D. Yang, and C. Bai. 2009. Potential effects of peroxisome proliferator-activated receptor activator on LPS-induced lung injury in rats. Pulmonary Pharmacology & Therapeutics 22(4): 318–325.

    Article  CAS  Google Scholar 

  9. Hardaker, E.L., M.S. Freeman, N. Dale, P. Bahra, F. Raza, K.H. Banner, and C. Poll. 2010. Exposing rodents to a combination of tobacco smoke and lipopolysaccharide results in an exaggerated inflammatory response in the lung. British Journal of Pharmacology 160(8): 1985–1996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ryu, H.W., H.-H. Song, I.-S. Shin, B.O. Cho, S.H. Jeong, D.-Y. Kim, K.-S. Ahn, and S.-R. Oh. 2015. Suffruticosol A isolated from Paeonia lactiflora seedcases attenuates airway inflammation in mice induced by cigarette smoke and LPS exposure. Journal of Functional Foods 17: 774–784.

    Article  CAS  Google Scholar 

  11. Milara, J., J. Lluch, P. Almudever, J. Freire, Q. Xiaozhong, and J. Cortijo. 2014. Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease. Journal of Allergy and Clinical Immunology 134(2): 314–322.

    Article  CAS  PubMed  Google Scholar 

  12. Bellaver, Bruna, D.G. Souza, D.O. Souza, and A. Quincozes-Santos. 2014. Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats. Toxicology in Vitro 28(4): 479–484.

    Article  CAS  PubMed  Google Scholar 

  13. Wang, D.-G., W.-Y. Liu, and G.-T. Chen. 2013. A simple method for the isolation and purification of resveratrol from Polygonum cuspidatum. Journal of Pharmaceutical Analysis 3(4): 241–247.

    Article  CAS  Google Scholar 

  14. Tang, W., J. Xie, S. Xu, H. Lv, M. Lin, S. Yuan, J. Bai, Q. Hou, and S. Yu. 2014. Novel nitric oxide-releasing derivatives of brusatol as anti- inflammatory agents: design, synthesis, biological evaluation, and nitric oxide release studies. Journal of Medicinal Chemistry 57(18): 7600–7612.

    Article  CAS  PubMed  Google Scholar 

  15. Voynow, J.A., B.M. Fischer, D.E. Malarkey, L.H. Burch, T. Wong, M. Longphre, S.B. Ho, and W.M. Foster. 2004. Neutrophil elastase induces mucus cell metaplasia in mouse lung. American Journal of Physiology Lung Cellular and Molecular Physiology 287(6): L1293–1302.

    Article  CAS  PubMed  Google Scholar 

  16. Chen, J., H. Zhou, J. Wang, B. Zhang, F. Liu, J. Huang, J. Li, J. Lin, J. Bai, and R. Liu. 2015. Therapeutic effects of resveratrol in a mouse model of HDM-induced allergic asthma. International Immunopharmacology 25(1): 43–48.

    Article  CAS  PubMed  Google Scholar 

  17. Klopfleisch, R. 2013. Multiparametric and semiquantitative scoring systems for the evaluation of mouse model histopathology—a systematic review. BMC Veterinary Research 123(9): 1–15.

    Google Scholar 

  18. Churg, A., M. Cosio, and J.L. Wright. 2008. Mechanisms of cigarette smoke-induced COPD: insights from animal models. American Journal of Physiology Lung Cellular and Molecular Physiology 83(4): 1385–1396.

    Google Scholar 

  19. Makinde, T., R.F. Murphy, and D.K. Agrawal. 2007. The regulatory role of TGF-beta in airway remodeling in asthma. Immunology and Cell Biology 85(5): 348–356.

    Article  CAS  PubMed  Google Scholar 

  20. Liu, R., J. Bai, G. Xu, L. Xuan, T. Zhang, A. Meng, and Q. Hou. 2013. Multi-allergen challenge stimulates steriod-resistant airway inflammation via NF-kappaB-mediated IL-8 expression. Inflammation 36(4): 845–854.

    Article  CAS  PubMed  Google Scholar 

  21. Chakir, Jamila, Joanne Shannon, Sophie Molet, Motonori Fukakusa, Jack Elias, Michel Laviolette, Louis-Philippe Boulet, and Q. Hamid. 2003. Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression. Journal of Allergy and Clinical Immunology 111(6): 1293–1298.

    Article  CAS  PubMed  Google Scholar 

  22. Neveu, W.A., J.L. Allard, D.M. Raymond, L.M. Bourassa, S.M. Burns, J.Y. Bunn, C.G. Irvin, D.A. Kaminsky, and M. Rincon. 2010. Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function. Respiratory Research 28(11): 1–10.

    Google Scholar 

  23. Linden, A., and M. Adachi. 2002. Neutrophilic airway inflammation and IL-17. Allergy 57(9): 769–775.

    Article  CAS  PubMed  Google Scholar 

  24. Neveu, W.A., J.L. Allard, D.M. Raymond, L.M. Bourassa, S.M. Burns, J.Y. Bunn, C.G. Irvin, D.A. Kaminsky, and M. Rincon. 2010. Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function. Respiratory Research 11: 28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fischer, B.M., E. Pavlisko, and J.A. Voynow. 2011. Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and inflammation. International Journal of COPD 1(6): 413–421.

    Article  CAS  Google Scholar 

  26. Kim, H.P., X. Wang, S.-J. Lee, M.-H. Huang, Y. Wan, S.W. Ryter, and A.M.K. Choi. 2008. Autophagic proteins regulate cigarette smoke induced apoptosis: protective role of heme oxygenase-1. Autophagy 4(7): 887–895.

    Article  CAS  PubMed  Google Scholar 

  27. Ryter, S.W., and A.M.K. Choi. 2010. Autophagy in the lung. Proceedings of the American Thoracic Society 7(10): 13–21.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shi, J., N. Yin, L.L. Xuan, C.S. Yao, A.M. Meng, and Q. Hou. 2012. Vam3, a derivative of resveratrol, attenuates cigarette smoke-induced autophagy. Acta Pharmacologica Sinica 33(7): 888–896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Knobloch, J., B. Sibbing, D. Jungck, Y. Lin, K. Urban, E. Stoelben, J. Strauch, and A. Koch. 2010. Resveratrol impairs the release of steroid-resistant inflammatory cytokines from human airway smooth muscle cells in chronic obstructive pulmonary disease. The Journal of Pharmacology and Experimental Therapeutics 335(3): 788–798.

    Article  CAS  PubMed  Google Scholar 

  30. Wood, Lisa G., P.A.B. Wark, and M.L. Garg. 2009. Antioxidant and anti-inflammatory effects of resveratrol in airway disease. Antioxidants & Redox Signaling 13(10): 1535–1548.

    Article  CAS  Google Scholar 

  31. Mikula-Pietrasik, J., A. Kuczmarska, M. Kucinska, M. Murias, M. Wierzchowski, M. Winckiewicz, R. Staniszewski, A. Breborowicz, and K. Ksiazek. 2012. Resveratrol and its synthetic derivatives exert opposite effects on mesothelial cell-dependent angiogenesis via modulating secretion of VEGF and IL-8/CXCL8. Angiogenesis 15(3): 361–376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lee, K.Y., J.Y. Jung, M.Y. Lee, D. Jung, E.S. Cho, and H.Y. Son. 2012. Diospyros blancoi attenuates asthmatic effects in a mouse model of airway inflammation. Inflammation 35(2): 623–632.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Jiangxi Province Education Office Youth Scientific Research Fund (No.GJJ14226) and Jiangxi Province Health and Family Planning Commission Fund (2014A070).

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Correspondence to Renping Liu.

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Chen, J., Yang, X., Zhang, W. et al. Therapeutic Effects of Resveratrol in a Mouse Model of LPS and Cigarette Smoke-Induced COPD. Inflammation 39, 1949–1959 (2016). https://doi.org/10.1007/s10753-016-0430-3

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  • DOI: https://doi.org/10.1007/s10753-016-0430-3

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