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Inflammation

pp 1–11 | Cite as

Curcumin Attenuates Airway Inflammation and Airway Remolding by Inhibiting NF-κB Signaling and COX-2 in Cigarette Smoke-Induced COPD Mice

  • Jin Yuan
  • Renping Liu
  • Yaohui Ma
  • Zhaoqiang Zhang
  • Zehao Xie
ORIGINAL ARTICLE

Abstract

The purpose of this study is to evaluate the therapeutic effects of curcumin on airway inflammation using LPS and cigarette smoke (LC)-induced COPD murine models and LPS-stimulated human bronchial epithelial (BEAS-2B) cells. In this research, COPD murine models were established after challenged with LPS for 2 days and exposed to cigarette smoke for 35 days. Treatment with curcumin for 10 days distinctly alleviated airway inflammation and airway remolding in LC-induced COPD mice according to the lung H&E histopathological examination. The number of neutrophils and lymphocytes in broncho alveolar lavage fluid (BALF) was significantly decreased in curcumin+LC-treated group compared with the LC-induced mice. Additionally, curcumin inhibited BEAS-2B cells proliferation, which suggested the preventive effect of curcumin on progressive airway remolding and inflammatory response mediated by bronchial epithelial cells. Further investigation demonstrated an underlying molecular mechanism for the therapeutic effects of curcumin may rely on the inhibition of the degradation of IκBα and COX-2 expression in curcumin+LC-treated COPD mice and LPS-stimulated BEAS-2B cells. Overall, curcumin alleviates the airway inflammation and airway remolding, which is closely related to inhibit the BEAS-2B cells proliferation and suppress the activation of NF-κB and COX-2 expression. These findings indicate that curcumin may be a potential agent for the therapy of COPD.

KEY WORDS

Curcumin COPD NF-κB COX-2 Inflammation 

Abbreviations

COPD

Chronic obstructive pulmonary disease

DEX

Dexamethasone

CUR

Curcumin

LPS

Lipopolysaccharide

BALF

Bronchoalveolar lavage fluid

PBS

Phosphate-buffered physiological saline

DMSO

Dimethyl sulfoxide

CS

Cigarette smoke

LC

LPS + cigarette smoke

NF-κB

Nuclear factor-κB

COX-2

Cyclooxygenase-2

IL-6

Interleukin 6

TGF-β

Transforming growth factor-β

BECs

Bronchial epithelial cells

Notes

Acknowledgments

This work was supported by the Department of Science and Technology Program Funds of Jiangxi Province, China (No. 20151BAB205085).

Compliance with Ethical Standards

The entire experiments were reviewed and proved by the Institutional Animal Experimental Ethics Committee of Nanchang University.

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Organization, W.H., WHO. 2013. the top 10 causes of death. Countries.Google Scholar
  2. 2.
    Yoshida, T., and R.M. Tuder. 2007. Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease. Physiological Reviews 87 (3): 1047–1082.CrossRefPubMedGoogle Scholar
  3. 3.
    Tamimi, 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 (3): 319–328.CrossRefPubMedGoogle Scholar
  4. 4.
    Mannino, D.M., and A.S. Buist. 2007. Global burden of COPD: Risk factors, prevalence, and future trends. The Lancet 370 (9589): 765–773.CrossRefGoogle Scholar
  5. 5.
    Rovina, N., A. Koutsoukou, and N.G. Koulouris. 2013. Inflammation and immune response in COPD: Where do we stand? Mediators of Inflammation 2013: 413735.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Hasday, J.D., R. Bascom, J.J. Costa, T. Fitzgerald, and W. Dubin. 1999. Bacterial endotoxin is an active component of cigarette smoke. Chest 115 (3): 829–835.CrossRefPubMedGoogle Scholar
  7. 7.
    Al-Harbi, N.O., et al. 2016. Dexamethasone attenuates LPS-induced acute lung injury through inhibition of NF-kappaB, COX-2, and pro-inflammatory mediators. Immunological Investigations 45 (4): 349–369.CrossRefPubMedGoogle Scholar
  8. 8.
    Di Stefano, A., et al. 2002. Increased expression of nuclear factor- B in bronchial biopsies from smokers and patients with COPD. European Respiratory Journal 20 (3): 556–563.CrossRefPubMedGoogle Scholar
  9. 9.
    Morita, I. 2002. Distinct functions of COX-1 and COX-2. Prostaglandins & Other Lipid Mediators 68-69: 165–175.CrossRefGoogle Scholar
  10. 10.
    Cheng, J., R.T. Dackor, J.A. Bradbury, H. Li, L.M. DeGraff, L.K. Hong, D. King, F.B. Lih, A. Gruzdev, M.L. Edin, G.S. Travlos, G.P. Flake, K.B. Tomer, and D.C. Zeldin. 2016. Contribution of alveolar type II cell-derived cyclooxygenase-2 to basal airway function, lung inflammation, and lung fibrosis. The FASEB Journal 30 (1): 160–173.CrossRefPubMedGoogle Scholar
  11. 11.
    Chen, Y., et al. 2008. Enhanced levels of prostaglandin E2 and matrix metalloproteinase-2 correlate with the severity of airflow limitation in stable COPD. Respirology 13 (7): 1014–1021.PubMedGoogle Scholar
  12. 12.
    Rumzhum, N.N., and A.J. Ammit. 2016. Cyclooxygenase 2: Its regulation, role and impact in airway inflammation. Clinical and Experimental Allergy 46 (3): 397–410.CrossRefPubMedGoogle Scholar
  13. 13.
    Brouk, B. 1975. Plants consumed by man. QUARTERLY REVIEW OF BIOLOGY.Google Scholar
  14. 14.
    Sharma, R.A., A.J. Gescher, and W.P. Steward. 2005. Curcumin: The story so far. European Journal of Cancer 41 (13): 1955–1968.CrossRefPubMedGoogle Scholar
  15. 15.
    Lee, I.T., and C.-M. Yang. 2013. Inflammatory signalings involved in airway and pulmonary diseases. Mediators of Inflammation 2013: 1–12.Google Scholar
  16. 16.
    Fan, Z., et al. 2014. The protective effects of curcumin on experimental acute liver lesion induced by intestinal ischemia-reperfusion through inhibiting the pathway of NF-kappaB in a rat model. Oxidative Medicine and Cellular Longevity 2014: 191624.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Ni, H., W. Jin, T. Zhu, J. Wang, B. Yuan, J. Jiang, W. Liang, and Z. Ma. 2015. Curcumin modulates TLR4/NF-kappaB inflammatory signaling pathway following traumatic spinal cord injury in rats. The Journal of Spinal Cord Medicine 38 (2): 199–206.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wang, J., et al. 2017. Regulation of type II collagen, matrix metalloproteinase-13 and cell proliferation by interleukin-1β is mediated by curcumin via inhibition of NF-κB signaling in rat chondrocytes. Molecular Medicine Reports.Google Scholar
  19. 19.
    Sharafkhaneh, A., S. Velamuri, V. Badmaev, C. Lan, and N. Hanania. 2007. The potential role of natural agents in treatment of airway inflammation. Therapeutic Advances in Respiratory Disease 1 (2): 105–120.CrossRefPubMedGoogle Scholar
  20. 20.
    Chen, J., X. Yang, W. Zhang, D. Peng, Y. Xia, Y. Lu, X. Han, G. Song, J. Zhu, and R. Liu. 2016. Therapeutic effects of resveratrol in a mouse model of LPS and cigarette smoke-induced COPD. Inflammation 39 (6): 1949–1959.CrossRefPubMedGoogle Scholar
  21. 21.
    Liu, R., P. Wang, C. Wu, J. Chen, C. Li, Y. Xie, Q. Wang, J. Liu, H. He, and J. Zhu. 2017. Therapeutic effects of Hedyotis diffusa Willd in a COPD mouse model challenged with LPS and smoke. Experimental and Therapeutic Medicine.Google Scholar
  22. 22.
    Robert, K. 2013. Multiparametric and semiquantitative scoring systems for the evaluation of mouse model histopathology—A systematic review. BMC Veterinary Research 9 (1): 123.CrossRefGoogle Scholar
  23. 23.
    Rajendrasozhan, S., J.W. Hwang, H. Yao, N. Kishore, and I. Rahman. 2010. Anti-inflammatory effect of a selective IκB kinase-beta inhibitor in rat lung in response to LPS and cigarette smoke. Pulmonary Pharmacology & Therapeutics 23 (3): 172–181.CrossRefGoogle Scholar
  24. 24.
    Anto, R.J., A. Mukhopadhyay, S. Shishodia, C.G. Gairola, and B.B. Aggarwal. 2002. Cigarette smoke condensate activates nuclear transcription factor-κB through phosphorylation and degradation of IκBα: Correlation with induction of cyclooxygenase-2. Carcinogenesis 23 (9): 1511–1518.CrossRefPubMedGoogle Scholar
  25. 25.
    Poynter, M.E., C.G. Irvin, and Y.M. Janssen-Heininger. 2003. A prominent role for airway epithelial NF-kappa B activation in lipopolysaccharide-induced airway inflammation. Journal of Immunology 170 (12): 6257–6265.CrossRefGoogle Scholar
  26. 26.
    Liu, W., H.L. Jiang, L.L. Cai, M. Yan, S.J. Dong, and B. Mao. 2016. Tanreqing injection attenuates lipopolysaccharide-induced airway inflammation through MAPK/NF-kappaB signaling pathways in rats model. Evidence-based Complementary and Alternative Medicine 2016: 5292346.PubMedPubMedCentralGoogle Scholar
  27. 27.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Shu, J., D. Li, H. Ouyang, J. Huang, Z. Long, Z. Liang, Y. Chen, Y. Chen, Q. Zheng, M. Kuang, H. Tang, J. Wang, and W. Lu. 2017. Comparison and evaluation of two different methods to establish the cigarette smoke exposure mouse model of COPD. Scientific Reports 7 (1): 15454.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Oh, S.W., J.Y. Cha, J.E. Jung, B.C. Chang, H.J. Kwon, B.R. Lee, and D.Y. Kim. 2011. Curcumin attenuates allergic airway inflammation and hyper-responsiveness in mice through NF-κB inhibition. Journal of Ethnopharmacology 136 (3): 414–421.CrossRefPubMedGoogle Scholar
  30. 30.
    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.CrossRefPubMedGoogle Scholar
  31. 31.
    Stockley, R.A. 2002. Neutrophils and the pathogenesis of COPD. Chest 121 (5): 151S–155S.CrossRefPubMedGoogle Scholar
  32. 32.
    Neveu, W.A., et al. 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 (1): 1–10.CrossRefGoogle Scholar
  33. 33.
    Kumari, A., D. Dash, and R. Singh. 2017. Curcumin inhibits lipopolysaccharide (LPS)-induced endotoxemia and airway inflammation through modulation of sequential release of inflammatory mediators (TNF-α and TGF-β1) in murine model. Inflammopharmacology 25 (3): 329–341.CrossRefPubMedGoogle Scholar
  34. 34.
    Gao, W., L. Li, Y. Wang, S. Zhang, I.M. Adcock, P.J. Barnes, M. Huang, and X. Yao. 2015. Bronchial epithelial cells: The key effector cells in the pathogenesis of chronic obstructive pulmonary disease? Respirology 20 (5): 722–729.CrossRefPubMedGoogle Scholar
  35. 35.
    Hernandez, M.L., B. Harris, J.C. Lay, P.A. Bromberg, D. Diaz-Sanchez, R.B. Devlin, S.R. Kleeberger, N.E. Alexis, and D.B. Peden. 2010. Comparative airway inflammatory response of normal volunteers to ozone and lipopolysaccharide challenge. Inhalation Toxicology 22 (8): 648–656.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Zhang, J., L. Wu, and J.M. Qu. 2011. Inhibited proliferation of human lung fibroblasts by LPS is through IL-6 and IL-8 release. Cytokine 54 (3): 289–295.CrossRefPubMedGoogle Scholar
  37. 37.
    Fan, X.Y., B. Chen, Z.S. Lu, Z.F. Jiang, and S.Q. Zhang. 2016. Poly-l-arginine acts synergistically with LPS to promote the release of IL-6 and IL-8 via p38/ERK signaling pathways in NCI-H292 cells. Inflammation 39 (1): 47–53.CrossRefPubMedGoogle Scholar
  38. 38.
    Pettersen, C.A., and K.B. Adler. 2002. Airways inflammation and COPD: Epithelial-neutrophil interactions. Chest 121 (5): 142S–150S.CrossRefPubMedGoogle Scholar
  39. 39.
    Randell, S.H. 2006. Airway epithelial stem cells and the pathophysiology of chronic obstructive pulmonary disease. Proceedings of the American Thoracic Society 3 (8): 718–725.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Cohen, L., X. E, J. Tarsi, T. Ramkumar, T.K. Horiuchi, R. Cochran, S. DeMartino, K.B. Schechtman, I. Hussain, M.J. Holtzman, M. Castro, and and the NHLBI Severe Asthma Research Program (SARP). 2007. Epithelial cell proliferation contributes to airway remodeling in severe asthma. American Journal of Respiratory and Critical Care Medicine 176 (2): 138–145.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Li, Q., and I.M. Verma. 2002. NF-kappaB regulation in the immune system. Nature Reviews. Immunology 2 (10): 725–734.CrossRefPubMedGoogle Scholar
  42. 42.
    Tak, P.P., and G.S. Firestein. 2001. NF-kappaB: A key role in inflammatory diseases. Journal of Clinical Investigation 107 (1): 7–11.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Ghosh, S., M.J. May, and E.B. Kopp. 1998. NF-kappa B and Rel proteins: Evolutionarily conserved mediators of immune responses. Annual Review of Immunology 16 (1): 225–260.CrossRefPubMedGoogle Scholar
  44. 44.
    Mizgerd, J.P., M.M. Lupa, and M.S. Spieker. 2004. NF-κB p50 facilitates neutrophil accumulation during LPS-induced pulmonary inflammation. BMC Immunology 5 (1): 10.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Wang, J.Y., L. Chen, Z. Zheng, Q. Wang, J. Guo, and L. Xu. 2012. Cinobufocini inhibits NF-kappaB and COX-2 activation induced by TNF-alpha in lung adenocarcinoma cells. Oncology Reports 27 (5): 1619–1624.PubMedGoogle Scholar
  46. 46.
    Willoughby, D.A., A.R. Moore, and P.R. Colville-Nash. 2000. COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease. The Lancet 355 (9204): 646–648.CrossRefGoogle Scholar
  47. 47.
    Soslow, R.A., A.J. Dannenberg, D. Rush, B.M. Woerner, K.N. Khan, J. Masferrer, and A.T. Koki. 2000. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89 (12): 2637–2645.CrossRefPubMedGoogle Scholar
  48. 48.
    Yu, M., D. Ives, and C.S. Ramesha. 1997. Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2. Journal of Biological Chemistry 272 (34): 21181–21186.CrossRefPubMedGoogle Scholar
  49. 49.
    Liu, H., A.M. Mamoon, and J.M. Farley Sr. 2005. Prostanoids secreted by alveolar macrophages enhance ionic currents in swine tracheal submucosal gland cells. The Journal of Pharmacology and Experimental Therapeutics 315 (2): 729–739.CrossRefPubMedGoogle Scholar
  50. 50.
    Park, G.Y., and J.W. Christman. 2006. Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases. American Journal of Physiology. Lung Cellular and Molecular Physiology 290 (5): L797–L805.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Profita, M., et al. 2010. Chronic obstructive pulmonary disease and neutrophil infiltration: Role of cigarette smoke and cyclooxygenase products. American Journal of Physiology. Lung Cellular and Molecular Physiology 298 (2): 261–269.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jin Yuan
    • 1
  • Renping Liu
    • 1
  • Yaohui Ma
    • 1
  • Zhaoqiang Zhang
    • 1
  • Zehao Xie
    • 1
  1. 1.Medical Experiment Education DepartmentMedical College of Nanchang UniversityNanchangChina

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