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Inflammation

, Volume 37, Issue 4, pp 1307–1316 | Cite as

Anti-inflammatory Effects of Triptolide in LPS-Induced Acute Lung Injury in Mice

  • Dong Wei
  • Zhihong Huang
Article

Abstract

Triptolide is one of the main active components of Chinese herb Tripterygium wilfordii Hook F, which has been demonstrated to have anti-inflammatory properties. The aim of this study was to investigate the effects of triptolide on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to clarify the possible mechanisms. Mice were administered intranasally with LPS to induce lung injury. Triptolide was administered intraperitoneally 1 h before LPS challenge. Triptolide-treated mice exhibited significantly reduced leukocyte, myeloperoxidase (MPO) activity, edema of the lung, as well as TNF-α, IL-1β, and IL-6 production in the bronchoalveolar lavage fluid compared with LPS-treated mice. Additionally, Western blot analysis showed that triptolide inhibited the phosphorylation of inhibitor-kappa B kinase-alpha (IκB-α), p65, nuclear factor kappa B (NF-κB), p38, extracellular receptor kinase (ERK), and Jun N-terminal kinase (JNK) and the expression of Toll-like receptor 4 (TLR4) caused by LPS. In conclusion, our results suggested that the promising anti-inflammatory mechanism of triptolide may be that triptolide activates peroxisome proliferation-activated receptor gamma (PPAR-γ), thereby attenuating an LPS-induced inflammatory response. Triptolide may be a promising potential therapeutic reagent for ALI treatment.

KEY WORDS

triptolide lipopolysaccharide (LPS) acute lung injury (ALI) MAPKs nuclear factor kappa B (NF-κB) TLR4 

Notes

Acknowledgments

This work was supported by Science and Technology Pillar Program of Hebei Province, China (Grant Number: 13227110D).

Conflict of Interest

All authors declare that they have no conflict of interest.

References

  1. 1.
    Basu, R.K., L.S. Chawla, D.S. Wheeler, and S.L. Goldstein. 2012. Renal angina: an emerging paradigm to identify children at risk for acute kidney injury. Pediatric Nephrology 27: 1067–1078.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Atabai, K., and M.A. Matthay. 2002. The pulmonary physician in critical care. 5: acute lung injury and the acute respiratory distress syndrome: definitions and epidemiology. Thorax 57: 452–458.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Fu, Y.H., B. Liu, X.S. Feng, F.Y. Li, D.J. Liang, Z.C. Liu, D.P. Li, Y.G. Cao, X.C. Zhang, N.S. Zhang, and Z.T. Yang. 2012. The effect of magnolol on the toll-like receptor 4/nuclear factor kappa B signaling pathway in lipopolysaccharide-induced acute lung injury in mice. European Journal of Pharmacology 689: 255–261.CrossRefGoogle Scholar
  4. 4.
    Zhang, B., Z.Y. Liu, Y.Y. Li, Y. Luo, M.L. Liu, H.Y. Dong, Y.X. Wang, Y. Liu, P.T. Zhao, F.G. Jin, and Z.C. Li. 2011. Antiinflammatory effects of matrine in LPS-induced acute lung injury in mice. European Journal of Pharmaceutical Sciences 44: 573–579.PubMedCrossRefGoogle Scholar
  5. 5.
    Wiedeman, H.P., A.P. Wheeler, and G.R. Bernard. 2007. Comparison of two fluid-management strategies in acute lung injury. Annals of Internal Medicine 147: 413–414.Google Scholar
  6. 6.
    Willson, D.F. 2005. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial (vol 293, pg 470, 2005). JAMA 294: 900.CrossRefGoogle Scholar
  7. 7.
    Mei, S.H.J., S.D. McCarter, Y.P. Deng, C.H. Parker, W.C. Liles, and D.J. Stewart. 2007. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PloS Medicine 4: 1525–1537.CrossRefGoogle Scholar
  8. 8.
    Ware, L.B., and M.A. Matthay. 2000. The acute respiratory distress syndrome. New England Journal of Medicine 342: 1334–1349.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee, W.L., and G.P. Downey. 2001. Neutrophil activation and acute lung injury. Current Opinion in Critical Care 7: 1–7.PubMedCrossRefGoogle Scholar
  10. 10.
    da Silva, Correia J., K. Soldau, U. Christen, P.S. Tobias, and R.J. Ulevitch. 2001. Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. Transfer from CD14 to TLR4 and MD-2. Journal of Biological Chemistry 276: 21129–21135.CrossRefGoogle Scholar
  11. 11.
    Nagai, Y., S. Akashi, M. Nagafuku, M. Ogata, Y. Iwakura, S. Akira, T. Kitamura, A. Kosugi, M. Kimoto, and K. Miyake. 2002. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nature Immunology 3: 667–672.PubMedGoogle Scholar
  12. 12.
    Akashi, S., Y. Nagai, H. Ogata, M. Oikawa, K. Fukase, S. Kusumoto, K. Kawasaki, M. Nishijima, S. Hayashi, M. Kimoto, and K. Miyake. 2001. Human MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition. International Immunology 13: 1595–1599.PubMedCrossRefGoogle Scholar
  13. 13.
    Tengchaisri, T., R. Chawengkirttikul, N. Rachaphaew, V. Reutrakul, R. Sangsuwan, and S. Sirisinha. 1998. Antitumor activity of triptolide against cholangiocarcinoma growth in vitro and in hamsters. Cancer Letters 133: 169–175.PubMedCrossRefGoogle Scholar
  14. 14.
    Wu, Y., J. Cui, X. Bao, S. Chan, D.O. Young, D. Liu, and P. Shen. 2006. Triptolide attenuates oxidative stress, NF-kappaB activation and multiple cytokine gene expression in murine peritoneal macrophage. International Journal of Molecular Medicine 17: 141–150.PubMedGoogle Scholar
  15. 15.
    Liu, M., J. Dong, Y. Yang, X. Yang, and H. Xu. 2005. Anti-inflammatory effects of triptolide loaded poly(d, l-lactic acid) nanoparticles on adjuvant-induced arthritis in rats. Journal of Ethnopharmacology 97: 219–225.PubMedCrossRefGoogle Scholar
  16. 16.
    Gong, Y., B. Xue, J. Jiao, L. Jing, and X. Wang. 2008. Triptolide inhibits COX-2 expression and PGE2 release by suppressing the activity of NF-kappaB and JNK in LPS-treated microglia. Journal of Neurochemistry 107: 779–788.PubMedCrossRefGoogle Scholar
  17. 17.
    Mao, H., X.R. Chen, Q. Yi, S.Y. Li, Z.L. Wang, and F.Y. Li. 2008. Mycophenolate mofetil and triptolide alleviating airway inflammation in asthmatic model mice partly by inhibiting bone marrow eosinophilopoiesis. International Immunopharmacology 8: 1039–1048.PubMedCrossRefGoogle Scholar
  18. 18.
    Liu, Q.Y., T.Y. Chen, G.Y. Chen, X.L. Shu, A. Sun, P.C. Ma, L.W. Lu, and X.T. Cao. 2007. Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-kappa B pathways. Molecular Immunology 44: 2686–2696.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhu, B., Y.J. Wang, C.F. Zhu, Y. Lin, X.L. Zhu, S. Wei, Y. Lu, and X.X. Cheng. 2010. Triptolide inhibits extracellular matrix protein synthesis by suppressing the Smad2 but not the MAPK pathway in TGF-beta 1-stimulated NRK-49 F cells. Nephrology, Dialysis, Transplantation 25: 3180–3191.PubMedCrossRefGoogle Scholar
  20. 20.
    Kanayama, T., S. Mamiya, T. Nishihara, and J. Nishikawa. 2003. Basis of a high-throughput method for nuclear receptor ligands. Journal of Biochemistry 133: 791–797.PubMedCrossRefGoogle Scholar
  21. 21.
    Meduri, G.U., G. Kohler, S. Headley, E. Tolley, F. Stentz, and A. Postlethwaite. 1995. Inflammatory cytokines in the BAL of patients with ARDS. Persistent elevation over time predicts poor outcome. Chest 108: 1303–1314.PubMedCrossRefGoogle Scholar
  22. 22.
    Medzhitov, R., and J.C. Kagan. 2006. Phosphoinositide-mediated adaptor recruitment controls toll-like receptor signaling. Cell 125: 943–955.PubMedCrossRefGoogle Scholar
  23. 23.
    Yadav, P.N., Z. Liu, and M.M. Rafi. 2003. A diarylheptanoid from lesser galangal (Alpinia officinarum) inhibits proinflammatory mediators via inhibition of mitogen-activated protein kinase, p44/42, and transcription factor nuclear factor-kappa B. Journal of Pharmacology and Experimental Therapeutics 305: 925–931.PubMedCrossRefGoogle Scholar
  24. 24.
    Chun, S.C., S.Y. Jee, S.G. Lee, S.J. Park, J.R. Lee, and S.C. Kim. 2007. Anti-inflammatory activity of the methanol extract of moutan cortex in LPS-activated Raw264.7 cells. Evidence-based Complementary and Alternative Medicine 4: 327–333.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Bouwmeester, T., A. Bauch, H. Ruffner, P.O. Angrand, G. Bergamini, K. Croughton, C. Cruciat, D. Eberhard, J. Gagneur, S. Ghidelli, et al. 2004. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature Cell Biology 6: 97–105.PubMedCrossRefGoogle Scholar
  26. 26.
    Wilson, S.J., B.A. Leone, D. Anderson, A. Manning, and S.T. Holgate. 1999. Immunohistochemical analysis of the activation of NF-kappaB and expression of associated cytokines and adhesion molecules in human models of allergic inflammation. Journal of Pathology 189: 265–272.PubMedCrossRefGoogle Scholar
  27. 27.
    Richmond, A. 2002. NF-kappa B, chemokine gene transcription and tumour growth. Nature Reviews Immunology 2: 664–674.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Karin, M., and Y. Ben-Neriah. 2000. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annual Review of Immunology 18: 621–663.PubMedCrossRefGoogle Scholar
  29. 29.
    Li, H., X.Z. Ruan, S.H. Powis, R. Fernando, W.Y. Mon, D.C. Wheeler, J.F. Moorhead, and Z. Varghese. 2005. EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: evidence for a PPAR-gamma-dependent mechanism. Kidney International 67: 867–874.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.College of Veterinary MedicineHebei North UniversityZhangjiakouPeople’s Republic of China

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