Skip to main content

Advertisement

SpringerLink
Log in

SeMet Mediates Anti-inflammation in LPS-Induced U937 Cells Targeting NF-κB Signaling Pathway

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

In previous studies, selenium (Se) was reported to play critical roles in anti-inflammatory activities. Nevertheless, limited information could be obtained during inflammation about selenomethionine (SeMet) in U937 human macrophage cells. The purpose of this study was to investigate the effects of SeMet on the inflammatory responses to lipopolysaccharide (LPS)-induced U937 macrophage cells and the signaling pathways targeted. U937 cells were pretreated with SeMet (1 μM) and subsequently induced with LPS (1 μg/ml) for 24 h. In the cell counting kit-8 assay (CCK-8), SeMet significantly inhibits the proliferation of U937 cells. SeMet also inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) stimulated by LPS. In the Western blot assay and real-time polymerase chain reaction (RT-PCR), SeMet significantly reduced protein expression and production of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and COX-2 in U937 cells. Furthermore, SeMet markedly suppressed the LPS-mediated activation of nuclear factor-kappa B (NF-κB) by blocking the degradation of inhibitor-κB proteins (IκBα) and lessening the translocations of P50 subunit content of NF-κB in the nucleus. These findings suggested the anti-inflammatory activity of SeMet in U937 cells; indicating that SeMet might be a potential treatment for inflammation therapy.

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. Chabane, N., N. Zayed, H. Afif, L. Mfuna-Endam, M. Benderdour, C. Boileau, J. Martel-Pelletier, J.P. Pelletier, N. Duval, and H. Fahmi. 2008. Histone deacetylase inhibitors suppress interleukin-1beta-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Osteoarthritis and Cartilage 16(10): 1267–1274.

    Article  CAS  PubMed  Google Scholar 

  2. Lee, A.K., S.H. Sung, Y.C. Kim, and S.G. Kim. 2003. Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-alpha and COX-2 expression by sauchinone effects on I-kappaBalpha phosphorylation, C/EBP and AP-1 activation. British Journal of Pharmacology 139(1): 11–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Katchamart, W., S. Johnson, H.J. Lin, V. Phumethum, C. Salliot, and C. Bombardier. 2010. Predictors for remission in rheumatoid arthritis patients: A systematic review. Arthritis Care & Research 62(8): 1128–1143.

    Article  Google Scholar 

  4. Allan, C.B., G.M. Lacourciere, and T.C. Stadtman. 1999. Responsiveness of selenoproteins to dietary selenium. Annual Review of Nutrition 19: 1–16.

    Article  CAS  PubMed  Google Scholar 

  5. Knekt, P., M. Heliovaara, K. Aho, G. Alfthan, J. Marniemi, and A. Aromaa. 2000. Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis. Epidemiology 11(4): 402–405.

    Article  CAS  PubMed  Google Scholar 

  6. Luth, H.J., M. Holzer, U. Gartner, M. Staufenbiel, and T. Arendt. 2001. Expression of endothelial and inducible NOS-isoforms is increased in Alzheimer’s disease, in APP23 transgenic mice and after experimental brain lesion in rat: Evidence for an induction by amyloid pathology. Brain Research 913(1): 57–67.

    Article  CAS  PubMed  Google Scholar 

  7. Rayman, M.P. 2000. The importance of selenium to human health. Lancet 356(9225): 233–241.

    Article  CAS  PubMed  Google Scholar 

  8. Hurwitz, B.E., J.R. Klaus, M.M. Llabre, A. Gonzalez, P.J. Lawrence, K.J. Maher, J.M. Greeson, M.K. Baum, G. Shor-Posner, J.S. Skyler, et al. 2007. Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: A randomized controlled trial. Archives of Internal Medicine 167(2): 148–154.

    Article  CAS  PubMed  Google Scholar 

  9. Schomburg, L., and J. Kohrle. 2008. On the importance of selenium and iodine metabolism for thyroid hormone biosynthesis and human health. Molecular Nutrition & Food Research 52(11): 1235–1246.

    Article  CAS  Google Scholar 

  10. Cao, Y.Z., C.C. Reddy, and L.M. Sordillo. 2000. Altered eicosanoid biosynthesis in selenium-deficient endothelial cells. Free Radical Biology and Medicine 28(3): 381–389.

    Article  CAS  PubMed  Google Scholar 

  11. Smith, A.D., L. Cheung, and S. Botero. 2011. Long-term selenium deficiency increases the pathogenicity of a Citrobacter rodentium infection in mice. Biological Trace Element Research 144(1–3): 965–982.

    Article  CAS  PubMed  Google Scholar 

  12. Andriamanalijaona, R., M. Kypriotou, C. Bauge, E. Renard, F. Legendre, M. Raoudi, K. Boumediene, H. Gatto, P. Monginoux, and J.P. Pujol. 2005. Comparative effects of 2 antioxidants, selenomethionine and epigallocatechin-gallate, on catabolic and anabolic gene expression of articular chondrocytes. Journal of Rheumatology 32(10): 1958–1967.

    CAS  PubMed  Google Scholar 

  13. Cheng, A.W., T.V. Stabler, M. Bolognesi, and V.B. Kraus. 2011. Selenomethionine inhibits IL-1beta inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes. Osteoarthritis and Cartilage 19(1): 118–125.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Roman-Blas, J.A., and S.A. Jimenez. 2006. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis and Cartilage 14(9): 839–848.

    Article  CAS  PubMed  Google Scholar 

  15. Hayden, M.S., and S. Ghosh. 2008. Shared principles in NF-kappaB signaling. Cell 132(3): 344–362.

    Article  CAS  PubMed  Google Scholar 

  16. Vallabhapurapu, S., and M. Karin. 2009. Regulation and function of NF-kappaB transcription factors in the immune system. Annual Review of Immunology 27: 693–733.

    Article  CAS  PubMed  Google Scholar 

  17. Baeuerle, P.A., and D. Baltimore. 1996. NF-kappa B: ten years after. Cell 87(1): 13–20.

    Article  CAS  PubMed  Google Scholar 

  18. 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(1–2): 115–127.

    Article  CAS  PubMed  Google Scholar 

  19. Sakaguchi, S., Y. Iizuka, S. Furusawa, Y. Tanaka, M. Takayanagi, and Y. Takayanagi. 2000. Roles of selenium in endotoxin-induced lipid peroxidation in the rats liver and in nitric oxide production in J774A.1 cells. Toxicology Letters 118(1–2): 69–77.

    Article  CAS  PubMed  Google Scholar 

  20. Prabhu, K.S., F. Zamamiri-Davis, J.B. Stewart, J.T. Thompson, L.M. Sordillo, and C.C. Reddy. 2002. Selenium deficiency increases the expression of inducible nitric oxide synthase in RAW 264.7 macrophages: Role of nuclear factor-kappaB in up-regulation. Biochemical Journal 366(Pt 1): 203–209.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Pleban, P.A., A. Munyani, and J. Beachum. 1982. Determination of selenium concentration and glutathione peroxidase activity in plasma and erythrocytes. Clinical Chemistry 28(2): 311–316.

    CAS  PubMed  Google Scholar 

  22. Ying, X., K. Yu, X. Chen, H. Chen, J. Hong, S. Cheng, and L. Peng. 2013. Piperine inhibits LPS induced expression of inflammatory mediators in RAW 264.7 cells. Cellular Immunology 285(1–2): 49–54.

    Article  CAS  PubMed  Google Scholar 

  23. Szasz, T., K. Thakali, G.D. Fink, and S.W. Watts. 2007. A comparison of arteries and veins in oxidative stress: Producers, destroyers, function, and disease. Experimental Biology and Medicine (Maywood, N.J.) 232(1): 27–37.

    CAS  Google Scholar 

  24. Gordon, S. 2003. Alternative activation of macrophages. Nature Reviews Immunology 3(1): 23–35.

    Article  CAS  PubMed  Google Scholar 

  25. Korhonen, R., A. Lahti, H. Kankaanranta, and E. Moilanen. 2005. Nitric oxide production and signaling in inflammation. Current Drug Targets. Inflammation and Allergy 4(4): 471–479.

    Article  CAS  PubMed  Google Scholar 

  26. Wu, G.J., T.G. Chen, H.C. Chang, W.T. Chiu, C.C. Chang, and R.M. Chen. 2007. Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes. Journal of Cellular Biochemistry 101(6): 1520–1531.

    Article  CAS  PubMed  Google Scholar 

  27. 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-Delta12,14-prostaglandin J2 in macrophages. Journal of Biological Chemistry 282(25): 17964–17973.

    Article  CAS  PubMed  Google Scholar 

  28. Chen, H., F. Ma, X. Hu, T. Jin, C. Xiong, and X. Teng. 2013. Elevated COX2 expression and PGE2 production by downregulation of RXRalpha in senescent macrophages. Biochemical and Biophysical Research Communications 440(1): 157–162.

    Article  CAS  PubMed  Google Scholar 

  29. Dray, A., and S.J. Read. 2007. Arthritis and pain. Future targets to control osteoarthritis pain. Arthritis Research and Therapy 9(3): 212.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Zamamiri-Davis, F., Y. Lu, J.T. Thompson, K.S. Prabhu, P.V. Reddy, L.M. Sordillo, and C.C. Reddy. 2002. Nuclear factor-kappaB mediates over-expression of cyclooxygenase-2 during activation of RAW 264.7 macrophages in selenium deficiency. Free Radical Biology and Medicine 32(9): 890–897.

    Article  CAS  PubMed  Google Scholar 

  31. 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(2): 381–386.

    Article  CAS  PubMed  Google Scholar 

  32. Ying, X., X. Chen, S. Cheng, Z. Zhao, X. Guo, H. Chen, J. Hong, L. Peng, and H. Xu. 2013. SeMet inhibits IL-1beta-induced rheumatoid fibroblast-like synoviocytes proliferation and the production of inflammatory mediators. Biological Trace Element Research 153(1–3): 437–445.

    Article  CAS  PubMed  Google Scholar 

  33. Stuhlmeier, K.M. 2007. The anti-rheumatic gold salt aurothiomalate suppresses interleukin-1beta-induced hyaluronan accumulation by blocking HAS1 transcription and by acting as a COX-2 transcriptional repressor. Journal of Biological Chemistry 282(4): 2250–2258.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study is supported in part by grants from National Natural Science Foundation of China (81371954 and 81171687), Zhejiang Natural Science Foundation (LQ12H06002), and the key project of Zhejiang Provincial Department of Science and Technology (2011C13033).

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, School of Medicine, The Second Affiliated Hospital, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China

    Yue Shen, Zhongli Shi, Tiao Lin, Hanxiao Zhu, Fanggang Bi, An Liu & Shigui Yan

  2. Department of Gynecologic Oncology, Women’s Reproductive Health Key Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, 310009, Zhejiang, China

    Shizhou Yang

  3. Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Xiaozhou Ying, Haixiao Liu & Kehe Yu

Authors
  1. Yue Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shizhou Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhongli Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tiao Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanxiao Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fanggang Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. An Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaozhou Ying
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Haixiao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kehe Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shigui Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yue Shen, Kehe Yu or Shigui Yan.

Additional information

Yue Shen and Shizhou Yang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, Y., Yang, S., Shi, Z. et al. SeMet Mediates Anti-inflammation in LPS-Induced U937 Cells Targeting NF-κB Signaling Pathway. Inflammation 38, 736–744 (2015). https://doi.org/10.1007/s10753-014-9984-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-014-9984-0

KEY WORDS

Search

Navigation