Inflammation Research

, Volume 62, Issue 5, pp 499–506 | Cite as

Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice

  • Zhicheng Liu
  • Zhengtao Yang
  • Yunhe Fu
  • Fenyang Li
  • Dejie Liang
  • Ershun Zhou
  • Xiaojing Song
  • Wen Zhang
  • Xichen Zhang
  • Yongguo Cao
  • Naisheng Zhang
Original Research Paper

Abstract

Objective

Gossypol has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice.

Methods

Male BALB/c mice were pretreated with gossypol 1 h before intranasal instillation of LPS. Then, 7 h after LPS administration, the myeloperoxidase in histology of lungs, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 were detected by western blot.

Results

Gossypol markedly attenuated the LPS-induced histological alterations in the lung and inhibited the production of TNF-α, IL-1β and IL-6. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS.

Conclusion

The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. Gossypol may be a promising potential therapeutic reagent for ALI treatment.

Keywords

Gossypol Lipopolysaccharide (LPS) Acute lung injury (ALI) Nuclear factor-kappa B (NF-κB) Mitogen-activated protein kinases (MAPKs) 

References

  1. 1.
    Rubenfeld GD. Epidemiology of acute lung injury. Crit Care Med. 2003;31:S276–84.PubMedCrossRefGoogle Scholar
  2. 2.
    Zhang X, Song K, Xiong H, Li H, Chu X, Deng X. Protective effect of florfenicol on acute lung injury induced by lipopolysaccharide in mice. Int Immunopharmacol. 2009;9:1525–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Atabai K, Matthay MA. The pulmonary physician in critical care. 5: acute lung injury and the acute respiratory distress syndrome: definitions and epidemiology. Thorax. 2002;57:452–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353:1685–93.PubMedCrossRefGoogle Scholar
  5. 5.
    Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;342:1334–49.PubMedCrossRefGoogle Scholar
  6. 6.
    Lee WL, Downey GP. Neutrophil activation and acute lung injury. Curr Opin Crit Care. 2001;7:1–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Coutinho EM. Gossypol: a contraceptive for men. Contraception. 2002;65:259–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Cui GH, Xu ZL, Yang ZJ, Xu YY, Xue SP. A combined regimen of gossypol plus methyltestosterone and ethinylestradiol as a contraceptive induces germ cell apoptosis and expression of its related genes in rats. Contraception. 2004;70:335–42.PubMedCrossRefGoogle Scholar
  9. 9.
    Ye W, Chang HL, Wang LS, Huang YW, Shu S, Sugimoto Y, et al. Induction of apoptosis by (−)-gossypol-enriched cottonseed oil in human breast cancer cells. Int J Mol Med. 2010;26:113–9.PubMedGoogle Scholar
  10. 10.
    Huang LH, Hu JQ, Tao WQ, Li YH, Li GM, Xie PY, et al. Gossypol inhibits phosphorylation of Bcl-2 in human leukemia HL-60 cells. Eur J Pharmacol. 2010;645:9–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Benhaim P, Mathes SJ, Hunt TK, Scheuenstuhl H, Benz CC. Induction of neutrophil Mac-1 integrin expression and superoxide production by the medicinal plant extract gossypol. Inflammation. 1994;18:443–58.PubMedCrossRefGoogle Scholar
  12. 12.
    Moon DO, Kim MO, Lee JD, Kim GY. Gossypol suppresses NF-kappaB activity and NF-kappaB-related gene expression in human leukemia U937 cells. Cancer Lett. 2008;264:192–200.PubMedCrossRefGoogle Scholar
  13. 13.
    Su CF, Yang FL, Chen HI. Inhibition of inducible nitric oxide synthase attenuates acute endotoxin-induced lung injury in rats. Clin Exp Pharmacol Physiol. 2007;34:339–46.PubMedCrossRefGoogle Scholar
  14. 14.
    Suda K, Tsuruta M, Eom J, Or C, Mui T, Jaw JE, et al. Acute lung injury induces cardiovascular dysfunction: effects of IL-6 and budesonide/formoterol. Am J Respir Cell Mol Biol. 2011;45:510–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Zmijewski JW, Lorne E, Zhao X, Tsuruta Y, Sha Y, Liu G, et al. Antiinflammatory effects of hydrogen peroxide in neutrophil activation and acute lung injury. Am J Respir Crit Care Med. 2009;179:694–704.PubMedCrossRefGoogle Scholar
  16. 16.
    Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol. 2004;202:145–56.PubMedCrossRefGoogle Scholar
  17. 17.
    Cribbs SK, Matthay MA, Martin GS. Stem cells in sepsis and acute lung injury. Crit Care Med. 2010;38:2379–85.PubMedCrossRefGoogle Scholar
  18. 18.
    Goodman RB, Pugin J, Lee JS, Matthay MA. Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev. 2003;14:523–35.PubMedCrossRefGoogle Scholar
  19. 19.
    Giebelen IA, van Westerloo DJ, LaRosa GJ, de Vos AF, van der Poll T. Local stimulation of alpha7 cholinergic receptors inhibits LPS-induced TNF-alpha release in the mouse lung. Shock. 2007;28:700–3.PubMedGoogle Scholar
  20. 20.
    Christman JW, Sadikot RT, Blackwell TS. The role of nuclear factor-kappa B in pulmonary diseases. Chest. 2000;117:1482–7.PubMedCrossRefGoogle Scholar
  21. 21.
    McCoy MK, Ruhn KA, Blesch A, Tansey MG. TNF: a key neuroinflammatory mediator of neurotoxicity and neurodegeneration in models of Parkinson’s disease. Adv Exp Med Biol. 2011;691:539–40.PubMedCrossRefGoogle Scholar
  22. 22.
    Kolliputi N, Waxman AB. IL-6 cytoprotection in hyperoxic acute lung injury occurs via PI3K/Akt-mediated Bax phosphorylation. Am J Physiol Lung Cell Mol Physiol. 2009;297:L6–16.PubMedCrossRefGoogle Scholar
  23. 23.
    Medzhitov R, Kagan JC. Phosphoinositide-mediated adaptor recruitment controls toll-like receptor signaling. Cell. 2006;125:943–55.PubMedCrossRefGoogle Scholar
  24. 24.
    Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006;25:6680–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Rao KM. MAP kinase activation in macrophages. J Leukoc Biol. 2001;69:3–10.PubMedGoogle Scholar
  26. 26.
    Jiang JX, Zhang Y, Ji SH, Zhu P, Wang ZG. Kinetics of mitogen-activated protein kinase family in lipopolysaccharide-stimulated mouse Kupffer cells and their role in cytokine production. Shock. 2002;18:336–41.PubMedCrossRefGoogle Scholar
  27. 27.
    Choi CY, Park KR, Lee JH, Jeon YJ, Liu KH, Oh S, et al. Isoeugenol suppression of inducible nitric oxide synthase expression is mediated by down-regulation of NF-kappaB, ERK1/2, and p38 kinase. Eur J Pharmacol. 2007;576:151–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Zhicheng Liu
    • 1
  • Zhengtao Yang
    • 1
  • Yunhe Fu
    • 1
  • Fenyang Li
    • 1
  • Dejie Liang
    • 1
  • Ershun Zhou
    • 1
  • Xiaojing Song
    • 1
  • Wen Zhang
    • 1
  • Xichen Zhang
    • 1
  • Yongguo Cao
    • 1
  • Naisheng Zhang
    • 1
  1. 1.Department of Clinical Veterinary Medicine, College of Animal Science and Veterinary MedicineJilin UniversityChangchunPeople’s Republic of China

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