Skip to main content

Advertisement

SpringerLink
Log in

Selenium Inhibits LPS-Induced Pro-inflammatory Gene Expression by Modulating MAPK and NF-κB Signaling Pathways in Mouse Mammary Epithelial Cells in Primary Culture

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Mastitis is characterized by an inflammation of the mammary gland of dairy animals and humans; this condition is one of the major causes of economic losses in dairy industries. Selenium (Se), a biological trace element, modulates the functions of many regulatory proteins in signal transduction and provides advantages for animals with inflammatory diseases, including mastitis. The current study aimed to assess the protective effects and the active mechanism of Na2SeO3 against lipopolysaccharide (LPS)-induced inflammation in mouse mammary epithelial cells (MMECs). Our results showed that LPS-induced expressions of cyclooxygenase-2 and tumor necrosis factor-α significantly decreased after Se was supplemented to Se-deficient MMECs. Na2SeO3 also suppressed LPS-induced nuclear factor-κB activation, inhibitory kappa B degradation, and ERK, JNK, and P38 phosphorylation in a dose-dependent manner. These results suggested that Se functions as an anti-inflammatory agent in mastitis.

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

Similar content being viewed by others

References

  1. Halasa, T., K. Huijps, O. Osteras, and H. Hogeveen. 2007. Economic effects of bovine mastitis and mastitis management: a review. Veterinary Quarterly 29: 18–318.

    Article  CAS  PubMed  Google Scholar 

  2. Salman, S., A. Khol-Parisini, H. Schafft, M. Lahrssen-Wiederholt, H.W. Hulan, D. Dinse, and J. Zentek. 2009. The role of dietary selenium in bovine mammary gland health and immune function. Animal Health Research Reviews 10: 21–34.

    Article  CAS  PubMed  Google Scholar 

  3. Miao, J., Y. Fa, B. Gu, W. Zhu, and S. Zou. 2012. Taurine attenuates lipopolysaccharide-induced dysfunction in mouse mammary epithelial cells. Cytokine 59: 35–40.

    Article  CAS  PubMed  Google Scholar 

  4. Duntas, L.H. 2009. Selenium and inflammation: Underlying anti-inflammatory mechanisms. Hormone and Metabolic Research 41: 443–447.

    Article  CAS  PubMed  Google Scholar 

  5. Goldammer, T., H. Zerbe, A. Molenaar, H.J. Schuberth, R.M. Brunner, S.R. Kata, and H.M. Seyfert. 2004. Mastitis increases mammary mRNA abundance of beta-defensin 5, toll-like-receptor 2 (TLR2), and TLR4 but not TLR9 in cattle. Clinical and Diagnostic Laboratory Immunology 11: 174–185.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Rainard, P. 2003. The complement in milk and defense of the bovine mammary gland against infections. Veterinary Research 34: 647–670.

    Article  CAS  PubMed  Google Scholar 

  7. Aitken, S.L., C.M. Corl, and L.M. Sordillo. 2011. Immunopathology of mastitis: Insights into disease recognition and resolution. Journal of Mammary Gland Biology and Neoplasia 16: 291–304.

    Article  PubMed  Google Scholar 

  8. Li, D., Y. Fu, W. Zhang, G. Su, B. Liu, M. Guo, F. Li, D. Liang, Z. Liu, X. Zhang, Y. Cao, N. Zhang, and Z. Yang. 2012. Salidroside attenuates inflammatory responses by suppressing nuclear factor-kappaB and mitogen activated protein kinases activation in lipopolysaccharide-induced mastitis in mice. Inflammation Research 62: 9–15.

    Article  PubMed  Google Scholar 

  9. Morita, I. 2002. Distinct functions of COX-1 and COX-2. Prostaglandins & Other Lipid Mediators 68–69: 165–175.

    Article  Google Scholar 

  10. Ceballos-Marquez, A., H.W. Barkema, H. Stryhn, J.J. Wichtel, J. Neumann, A. Mella, J. Kruze, M.S. Espindola, and F. Wittwer. 2010. The effect of selenium supplementation before calving on early-lactation udder health in pastured dairy heifers. Journal of Dairy Science 93: 4602–4612.

    Article  CAS  PubMed  Google Scholar 

  11. Kiremidjian-Schumacher, L., M. Roy, H.I. Wishe, M.W. Cohen, and G. Stotzky. 1994. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biological Trace Element Research 41: 115–127.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang, F., W. Yu, J.L. Hargrove, P. Greenspan, R.G. Dean, E.W. Taylor, and D.K. Hartle. 2002. Inhibition of TNF-alpha induced ICAM-1, VCAM-1 and E-selectin expression by selenium. Atherosclerosis 161: 381–386.

    Article  CAS  PubMed  Google Scholar 

  13. Kim, S.H., V.J. Johnson, T.Y. Shin, and R.P. Sharma. 2004. Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and NF-kappaB signaling pathways. Experimental Biology and Medicine (Maywood, N.J.) 229: 203–213.

    CAS  Google Scholar 

  14. Vunta, H., B.J. Belda, R.J. Arner, R.C. Channa, H.J. Vanden, and P.K. Sandeep. 2008. Selenium attenuates pro-inflammatory gene expression in macrophages. Molecular Nutrition & Food Research 52: 1316–132.

    Article  CAS  Google Scholar 

  15. Ciliberto, G., R. Arcone, E.F. Wagner, and U. Ruther. 1987. Inducible and tissue-specific expression of human C-reactive protein in transgenic mice. EMBO Journal 6: 4017–4022.

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Ogata, S., Y. Kubota, T. Yamashiro, H. Takeuchi, T. Ninomiya, Y. Suyama, and K. Shirasuna. 2007. Signaling pathways regulating IL-1alpha-induced COX-2 expression. Journal of Dental Research 86: 186–191.

    Article  CAS  PubMed  Google Scholar 

  17. Ip, M.M., P.A. Masso-Welch, S.F. Shoemaker, W.K. Shea-Eaton, and C. Ip. 1999. Conjugated linoleic acid inhibits proliferation and induces apoptosis of normal rat mammary epithelial cells in primary culture. Experimental Cell Research 250: 22–34.

    Article  CAS  PubMed  Google Scholar 

  18. Fernandes, J.B., L.G. Zanardo, N.N. Galvao, I.A. Carvalho, L.A. Nero, and M.A. Moreira. 2011. Escherichia coli from clinical mastitis: Serotypes and virulence factors. Journal of Veterinary Diagnostic Investigation 23: 1146–1152.

    Article  PubMed  Google Scholar 

  19. Petzl, W., J. Gunther, T. Pfister, C. Sauter-Louis, L. Goetze, S. von Aulock, A. Hafner-Marx, H.J. Schuberth, H.M. Seyfert, and H. Zerbe. 2012. Lipopolysaccharide pretreatment of the udder protects against experimental Escherichia coli mastitis. Innate Immunity 18: 467–477.

    Article  CAS  PubMed  Google Scholar 

  20. Strandberg, Y., C. Gray, T. Vuocolo, L. Donaldson, M. Broadway, and R. Tellam. 2005. Lipopolysaccharide and lipoteichoic acid induce different innate immune responses in bovine mammary epithelial cells. Cytokine 31: 72–86.

    Article  CAS  PubMed  Google Scholar 

  21. Schmitz, S., M.W. Pfaffl, H.H. Meyer, and R.M. Bruckmaier. 2004. Short-term changes of mRNA expression of various inflammatory factors and milk proteins in mammary tissue during LPS-induced mastitis. Domestic Animal Endocrinology 26: 111–126.

    Article  CAS  PubMed  Google Scholar 

  22. Persson, W.K., I.G. Colditz, S. Lun, and K. Ostensson. 2003. Cytokines in mammary lymph and milk during endotoxin-induced bovine mastitis. Research in Veterinary Science 74: 31–36.

    Article  Google Scholar 

  23. Havell, E.A. 1989. Evidence that tumor necrosis factor has an important role in antibacterial resistance. Journal of Immunology 143: 2894–2899.

    CAS  Google Scholar 

  24. Slebodzinski, A.B., E. Malinowski, and W. Lipczak. 2002. Concentrations of triiodothyronine (T3), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in milk from healthy and naturally infected quarters of cows. Research in Veterinary Science 72: 17–21.

    Article  CAS  PubMed  Google Scholar 

  25. Persson Waller, K., I.G. Colditz, S. Lun, and K. Ostensson. 2003. Cytokines in mammary lymph and milk during endotoxin-induced bovine mastitis. Research in Veterinary Science 74: 31–36.

    Article  CAS  PubMed  Google Scholar 

  26. Zhang, H., and A.C. Issekutz. 2002. Down-modulation of monocyte transendothelial migration and endothelial adhesion molecule expression by fibroblast growth factor: Reversal by the anti-angiogenic agent SU6668. American Journal of Pathology 160: 2219–2230.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Yamanaka, H., K. Hisaeda, K. Hagiwara, R. Kirisawa, and H. Iwai. 2000. ELISA for bovine interleukin-1 receptor antagonist and its application to mastitic sera and whey. Journal of Veterinary Medical Science 62: 661–664.

    Article  CAS  PubMed  Google Scholar 

  28. Ohtsuka, H., K. Kudo, K. Mori, F. Nagai, A. Hatsugaya, M. Tajima, K. Tamura, F. Hoshi, M. Koiwa, and S. Kawamura. 2001. Acute phase response in naturally occurring coliform mastitis. Journal of Veterinary Medical Science 63: 675–678.

    Article  CAS  PubMed  Google Scholar 

  29. Zhang, F., W. Yu, J.L. Hargrove, P. Greenspan, R.G. Dean, E.W. Taylor, and D.K. Hartle. 2002. Inhibition of TNF-alpha induced ICAM-1, VCAM-1 and E-selectin expression by selenium. Atherosclerosis 161: 381–386.

    Article  CAS  PubMed  Google Scholar 

  30. Croffor, L.J. 1997. COX-1 and COX-2 tissue expression: Implications and predictions. Journal of Rheumatology. Supplement 49: 15–19.

    Google Scholar 

  31. Pfaffl, M.W., S.L. Wittmann, H.H. Meyer, and R.M. Bruckmaier. 2003. Gene expression of immunologically important factors in blood cells, milk cells, and mammary tissue of cows. Journal of Dairy Science 86: 538–545.

    Article  CAS  PubMed  Google Scholar 

  32. Vunta, H., F. Davis, U.D. Palempalli, D. Bhat, R.J. Arner, J.T. Thompson, D.G. Peterson, C.C. Reddy, and K.S. Prabhu. 2007. The anti-inflammatory effects of selenium are mediated through 15-deoxy-Δ12,14-prostaglandin J2 in macrophages. Journal of Biological Chemistry 282: 17964–17973.

    Article  CAS  PubMed  Google Scholar 

  33. Godowski, P.J. 2005. A smooth operator for LPS responses. Nature Immunology 6: 544–546.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (nos. 30972222, 3120195) and the Research Fund for the Doctoral Program of Higher Education of China (nos. 20110061130010, 20120061120098).

Conflict of interest

None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.

Author information

Authors and Affiliations

  1. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 130062, Jilin, People’s Republic of China

    Wen Zhang, Tiancheng Wang, Haichao Jiang, Mengyao Guo, Ershun Zhou, Yong Sun, Zhengtao Yang, Yongguo Cao & Naisheng Zhang

  2. Institute of Special Economic Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, Jilin, People’s Republic of China

    Runxiang Zhang

  3. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northeast Agriculture University, Harbin, 150030, Heilongjiang, People’s Republic of China

    Shiwen Xu

Authors
  1. Wen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Runxiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tiancheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haichao Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mengyao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ershun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yong Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhengtao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shiwen Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yongguo Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Naisheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yongguo Cao or Naisheng Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, W., Zhang, R., Wang, T. et al. Selenium Inhibits LPS-Induced Pro-inflammatory Gene Expression by Modulating MAPK and NF-κB Signaling Pathways in Mouse Mammary Epithelial Cells in Primary Culture. Inflammation 37, 478–485 (2014). https://doi.org/10.1007/s10753-013-9761-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-013-9761-5

KEY WORDS

Search

Navigation