Skip to main content
SpringerLink
Log in

Protective Effect of Naringenin Against Lipopolysaccharide-Induced Injury in Normal Human Bronchial Epithelium via Suppression of MAPK Signaling

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The present study aimed to evaluate the effect of naringenin on protection in lipopolysaccharide (LPS)-induced injury in normal human bronchial epithelium (NHBE) and to provide insights into the possible underlying mechanisms. NHBE were stimulated by LPS in the presence or absence of the narigenin. In vitro treatment with naringenin led to a significant attenuation in the LPS-induced NHBE secretion of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), superoxidase dismutase (SOD), nitricoxide synthase (NOS), myeloperoxidase (MPO), and nitric oxide (NO). RT-qPCR demonstrated that naringenin significantly reduced the LPS-induced upregulation of TNF-α, IL-6, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 mRNA expression in a dose-dependent manner. Additionally, Western blot analysis revealed that naringenin effectively suppressed NF-κB activation by inhibiting the degradation of IκB-α and the translocation of p65. Naringenin also attenuated mitogen-activated protein kinase (MAPK) activation by inhibiting the phosphorylation of ERK1/2, c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK. Taken together, these demonstrate that naringenin reduces TNF-α and IL-6 secretion and mRNA expression, possibly by blocking the activation of the NF-κB and MAPK signaling pathways in LPS-treated NHBE. These results indicated that naringenin had a protective effect on LPS-induced injury in NHBE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Venkayya, R., M. Lam, M. Willkom, G. Grünig, D.B. Corry, and D.J. Erle. 2002. The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells. American Journal of Respiratory Cell and Molecular Biology 26: 202–208.

    Article  CAS  PubMed  Google Scholar 

  2. Hamilton, L.M., D.E. Davies, S.J. Wilson, I. Kimber, R.J. Dearman, and S.T. Holgate. 2001. The bronchial epithelium in asthma-much more than a passive barrier. Monaldi Archives for Chest Disease 56: 48–54.

    CAS  PubMed  Google Scholar 

  3. Holgate, S.T. 2000. Epithelial damage and response. Clinical and Experimental Allergy 30: 37–41.

    Article  PubMed  Google Scholar 

  4. Velden, V.H., and H.F. Versnel. 1998. Bronchial epithelium: morphology, function and pathophysiology in asthma. European Cytokine Network 9: 585–597.

    CAS  PubMed  Google Scholar 

  5. Moon, D.O., C.M. Lee, J.H. Kang, B.H. Kim, Y.H. Oh, and Y.M. Park. 2004. Epigallocatechin-3-gallate, constituent of green tea, suppresses the LPS-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and NF-kappaB. Biochemical and Biophysical Research Communications 313: 148–155.

    Article  PubMed  Google Scholar 

  6. John, E., P. Pais, N. Furtado, A. Chin, J. Radhakrishnan, L. Fornell, A. Lumpaopong, and U.H. Beier. 2008. Early effects of lipopolysaccharide on cytokine release, hemodynamic and renal function in newborn piglets. Neonatology 93: 106–112.

    Article  CAS  PubMed  Google Scholar 

  7. Rogers, J., I. Perkins, O.A. Van, N. Burdash, T.W. Klein, and H. Friedman. 2005. Epigallocatechin gallate modulates cytokine production by bone marrow-derived dendritic cells stimulated with lipopolysaccharide or muramyldipeptide, or infected with Legionella pneumophila. Experimental Biology and Medicine 230: 645–651.

    CAS  PubMed  Google Scholar 

  8. Hallstrand, T.S., T.L. Hackett, W.A. Altemeier, G. Matute-Bello, P.M. Hansbro, and D.A. Knight. 2014. Airway epithelial regulation of pulmonary immune homeostasis and inflammation. Clinical Immunology 151: 1–15.

    Article  CAS  PubMed  Google Scholar 

  9. Bhargava, R., W. Janssen, C. Altmann, A. Andres-Hernando, K. Okamura, R.W. Vandivier, N. Ahuja, and S. Faubel. 2013. Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice. PLos ONE 8: e61405.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Lauder, S.N., E. Jones, K. Smart, A. Bloom, A.S. Williams, J.P. Hindley, B. Ondondo, P.R. Taylor, M. Clement, C. Fielding, A.J. Godkin, S.A. Jones, and A.M. Gallimore. 2013. Interleukin-6 limits influenza-induced inflammation and protects against fatal lung pathology. European Journal of Immunology 43: 2613–2625.

    Article  CAS  PubMed  Google Scholar 

  11. Berry, M., C. Brightling, I. Pavord, and A. Wardlaw. 2007. TNF-alpha in asthma. Current Opinion in Pharmacology 7: 279–282.

    Article  CAS  PubMed  Google Scholar 

  12. Brightling, C., M. Berry, and Y. Amrani. 2008. Targeting TNF-alpha: a novel therapeutic approach for asthma. Journal of Allergy and Clinical Immunology 121: 5–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Koch, L., B. Fritzsching, D. Frommhold, and J. Poeschl. 2011. Lipopolysaccharide-induced expression of Th1/Th2 cytokines in whole neonatal cord and adult blood: role of nuclear factor-kappa B and p38 MAPK. Neonatology 99: 140–145.

    Article  CAS  PubMed  Google Scholar 

  14. Abraham, E. 2000. NF-kappa B activation. Critical Care Medicine 28: 100–104.

    Article  Google Scholar 

  15. Nanashima, N., M. Akita, T. Yamada, T. Shimizu, H. Nakano, Y. Fan, and S. Tsuchida. 2008. The hairless phenotype of the Hirosaki hairless rat is due to the deletion of an 80-kb genomic DNA containing five basic keratin genes. Journal of Biological Chemistry 283: 16868–16875.

    Article  CAS  PubMed  Google Scholar 

  16. Jain, A., A. Yadav, A.I. Bozhkov, V.I. Padalko, and S.J. Flora. 2011. Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats. Ecotoxicology and Environmental Safety 74: 607–614.

    Article  CAS  PubMed  Google Scholar 

  17. Hirai, S., Y.I. Kim, T. Goto, M.S. Kang, M. Yoshimura, A. Obata, R. Yu, and T. Kawada. 2007. Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages. Life Sciences 81: 1272–1279.

    Article  CAS  PubMed  Google Scholar 

  18. Dou, W., J. Zhang, A. Sun, E. Zhang, L. Ding, S. Mukherjee, X. Wei, G. Chou, Z.T. Wang, and S. Mani. 2013. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling. British Journal of Nutrition 110: 599–608.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Lyu, S.Y., and W.B. Park. 2005. Production of cytokine and NO by RAW 264.7 macrophages and PBMC in vitro incubation with flavonoids. Archives of Pharmacal Research 28: 573–581.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to M.D. Xin Jin for assistance with statistical analysis.

Author information

Authors and Affiliations

  1. Soochow University Affiliated Children’s Hospital, Jingde Road 303#, Suzhou, Jiangsu Province, 215003, People’s Republic of China

    Dan-hong Yu & Chen-mei Mao

  2. Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Tongjia xiang 24#, Nanjing, Jiangsu Province, 210009, People’s Republic of China

    Chun-hua Ma

  3. Jiangsu Provincial Key Laboratory of Efficacy and Safety Evaluation of Traditional Chinese Medicine, College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province, 210046, People’s Republic of China

    Zhi-qiang Yue

  4. Department of Pharmacy, First Affiliated Hospital of Soochow University, Shizi Street 188#, Suzhou, Jiangsu Province, 215006, People’s Republic of China

    Xin Yao

Authors
  1. Dan-hong Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-hua Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhi-qiang Yue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chen-mei Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chen-mei Mao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Dh., Ma, Ch., Yue, Zq. et al. Protective Effect of Naringenin Against Lipopolysaccharide-Induced Injury in Normal Human Bronchial Epithelium via Suppression of MAPK Signaling. Inflammation 38, 195–204 (2015). https://doi.org/10.1007/s10753-014-0022-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-014-0022-z

KEY WORDS

Search

Navigation