Skip to main content
Log in

IFN-τ Alleviates Lipopolysaccharide-Induced Inflammation by Suppressing NF-κB and MAPKs Pathway Activation in Mice

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

IFN-τ, which is a type I interferon with low cytotoxicity, is defined as a pregnancy recognition signal in ruminants. Type I interferons have been used as anti-inflammatory agents, but their side effects limit their clinical application. The present study aimed to determine the anti-inflammatory effects of IFN-τ in a lipopolysaccharide-stimulated acute lung injury (ALI) model and in RAW264.7 cells and to confirm the mechanism of action involved. The methods used included histopathology, measuring the lung wet/dry ratio, determining the myeloperoxidase activity, ELISA, qPCR, and western blot. The results revealed that IFN-τ greatly ameliorated the infiltration of inflammatory cells and the expression of TNF-α, IL-1β, and IL-6. Further analysis revealed that IFN-τ down-regulated the expression of TLR-2 and TLR-4 mRNA and the activity of the NF-κB and MAPK pathways both in a lipopolysaccharide-induced ALI model and in RAW264.7 cells. The results demonstrated that IFN-τ suppressed the levels of pro-inflammatory cytokines by inhibiting the phosphorylation of the NF-κB and MAPK pathways. Thus, IFN-τ may be an optimal target for the treatment of inflammatory diseases.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Saugandhika, S., V. Sharma, H. Malik, et al. 2015. Expression and purification of buffalo interferon-tau and efficacy of recombinant buffalo interferon-tau for in vitro embryo development. Cytokine 75: 186–196.

    Article  CAS  PubMed  Google Scholar 

  2. Chethan, S.G., S.K. Singh, J. Nongsiej, et al. 2014. IFN-tau acts in a dose-dependent manner on prostaglandin production by buffalo endometrial stromal cells cultured in vitro. Reproduction in Domestic Animals 49: 403–408.

    Article  CAS  PubMed  Google Scholar 

  3. LeMessurier, K.S., H. Hacker, L. Chi, E. Tuomanen, and V. Redecke. 2013. Type I interferon protects against pneumococcal invasive disease by inhibiting bacterial transmigration across the lung. PLoS Pathogens 9, e1003727.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Gough, D.J., N.L. Messina, C.J.P. Clarke, R.W. Johnstone, and D.E. Levy. 2012. Constitutive Type I interferon modulates homeostatic balance through tonic signaling. Immunity 36: 166–174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cho, H., and B.L. Kelsall. 2014. The role of type I interferons in intestinal infection, homeostasis, and inflammation. Immunology Reviews 260: 145–167.

    Article  CAS  Google Scholar 

  6. Bartol, F.F., R.M. Roberts, F.W. Bazer, G.S. Lewis, J.D. Godkin, and W.W. Thatcher. 1985. Characterization of proteins produced in vitro by periattachment bovine conceptuses. Biology of Reproduction 32: 681–693.

    Article  CAS  PubMed  Google Scholar 

  7. Alexenko, A.P., A.D. Ealy, and R.M. Roberts. 1999. The cross-species antiviral activities of different IFN-tau subtypes on bovine, murine, and human cells: contradictory evidence for therapeutic potential. Journal of Interferon & Cytokine Research 19: 1335–1341.

    Article  CAS  Google Scholar 

  8. Bazer, F.W., J. Kim, G. Song, H. Ka, C.D. Tekwe, and G. Wu. 2012. Select nutrients, progesterone, and interferon tau affect conceptus metabolism and development. Annals of the New York Academy of Sciences 1271: 88–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ying, W., S. Kanameni, C.A. Chang, V. Nair, S. Safe, F.W. Bazer, and B.Y. Zhou. 2014. Interferon tau alleviates obesity-induced adipose tissue inflammation and insulin resistance by regulating macrophage polarization. PloS One 9: 1–17.

    Google Scholar 

  10. Hara, K., K. Shirasuna, F. Usui, et al. 2014. Interferon-tau attenuates uptake of nanoparticles and secretion of interleukin-1beta in macrophages. PloS One 9, e113974.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhang, S.Y., L.T. Xu, A.X. Li, and S.M. Wang. 2015. Effects of ergosterol, isolated from scleroderma polyrhizum pers., on lipopolysaccharide-induced inflammatory responses in acute lung injury. Inflammation 38: 1979–1985.

    Article  CAS  PubMed  Google Scholar 

  12. Conti, G., S. Tambalo, G. Villetti, et al. 2010. Evaluation of lung inflammation induced by intratracheal administration of LPS in mice: comparison between MRI and histology. Magnetic Resonance Materials in Physics 23: 93–101.

    Article  CAS  Google Scholar 

  13. Wang, Y., Q. Tu, W. Yan, et al. 2015. CXC195 suppresses proliferation and inflammatory response in LPS-induced human hepatocellular carcinoma cells via regulating TLR4-MyD88-TAK1-mediated NF-kappaB and MAPK pathway. Biochemical and Biophysical Research Communications 456: 373–379.

    Article  CAS  PubMed  Google Scholar 

  14. Damjanovic, D., A. Khera, M.F. Medina, et al. 2014. Type 1 interferon gene transfer enhances host defense against pulmonary Streptococcus pneumoniae infection via activating innate leukocytes. Molecular Therapy Methods & Clinical Development 1(5): 1–11.

    CAS  Google Scholar 

  15. Chon, T.W., and S. Bixler. 2010. Interferon-tau: current applications and potential in antiviral therapy. Journal of Interferon & Cytokine Research 30: 477–485.

    Article  CAS  Google Scholar 

  16. Soos, J.M., P.S. Subramaniam, A.C. Hobeika, J. Schiffenbauer, and H.M. Johnson. 1995. The IFN pregnancy recognition hormone IFN-tau blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity. Journal of Immunology 155: 2747–2753.

    CAS  Google Scholar 

  17. Do-Umehara, H.C., C. Chen, D. Urich, et al. 2013. Suppression of inflammation and acute lung injury by Miz1 via repression of C/EBP-delta. Nature Immunology 14: 461–469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kim, Y.J., J.H. Kim, K.J. Lee, et al. 2015. Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages. PloS One 10, e0120840.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Xu, X., P. Yin, C. Wan, et al. 2014. Punicalagin inhibits inflammation in LPS-induced RAW264.7 macrophages via the suppression of TLR4-mediated MAPKs and NF-kappaB activation. Inflammation 37: 956–965.

    Article  CAS  PubMed  Google Scholar 

  20. Tao, W.W., Q. Su, H.Q. Wang, et al. 2015. Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro. International Immunopharmacology 27: 138–147.

    Article  CAS  PubMed  Google Scholar 

  21. Roberts, R.M., A.D. Ealy, A.P. Alexenko, C.S. Han, and T. Ezashi. 1999. Trophoblast interferons. Placenta 20: 259–264.

    Article  CAS  PubMed  Google Scholar 

  22. Roberts, R.M. 2007. Interferon-tau, a Type 1 interferon involved in maternal recognition of pregnancy. Cytokine & Growth Factor 18: 403–408.

    Article  CAS  Google Scholar 

  23. Li, D., Y. Fu, W. Zhang, et al. 2013. 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  CAS  PubMed  Google Scholar 

  24. Gonzalez-Navajas, J.M., J. Lee, M. David, and E. Raz. 2012. Immunomodulatory functions of type I interferons. Nature Reviews Immunology 12: 125–135.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Yan, B., S. Ye, G. Chen, M. Kuang, N. Shen, and S. Chen. 2008. Dysfunctional CD4+, CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. Arthritis and Rheumatism 58: 801–812.

    Article  CAS  PubMed  Google Scholar 

  26. Namdar, A., B. Nikbin, M. Ghabaee, A. Bayati, and M. Izad. 2010. Effect of IFN-beta therapy on the frequency and function of CD4(+)CD25(+) regulatory T cells and Foxp3 gene expression in relapsing-remitting multiple sclerosis (RRMS): a preliminary study. Journal of Neuroimmunology 218: 120–124.

    Article  CAS  PubMed  Google Scholar 

  27. Sleijfer, S., M. Bannink, A.R. VanGool, W.H.J. Kruit, and G. Stoter. 2005. Side effects of interferon-alpha therapy. Pharmacy World and Science 27: 423–431.

    Article  CAS  PubMed  Google Scholar 

  28. Trinchieri, G. 2010. Type I interferon: friend or foe? The Journal of Experimental Medicine 207: 2053–2063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chen, X., J.S. Miao, H. Wang, et al. 2015. The anti-inflammatory activities of Ainsliaea fragrans Champ. extract and its components in lipopolysaccharide-stimulated RAW264.7 macrophages through inhibition of NF-kappa B pathway. Journal of Ethnopharmacology 170: 72–80.

    Article  CAS  PubMed  Google Scholar 

  30. Rauch, I., M. Muller, and T. Decker. 2013. The regulation of inflammation by interferons and their STATs. JAK-STAT 2, e23820.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wang, J., Y.T. Liu, L. Xiao, L. Zhu, Q. Wang, and T. Yan. 2014. Anti-inflammatory effects of apigenin in lipopolysaccharide-induced inflammatory in acute lung injury by suppressing COX-2 and NF-kB pathway. Inflammation 37: 2085–2090.

    Article  CAS  PubMed  Google Scholar 

  32. Seifart, C., A. Dempfle, A. Plagens, et al. 2005. TNF-alpha-, TNF-beta-, IL-6-, and IL-10-promoter polymorphisms in patients with chronic obstructive pulmonary disease. Tissue Antigens 65: 93–100.

    Article  CAS  PubMed  Google Scholar 

  33. Xu, D., M. Chen, X. Ren, X. Ren, and Y. Wu. 2014. Leonurine ameliorates LPS-induced acute kidney injury via suppressing ROS-mediated NF-kappaB signaling pathway. Fitoterapia 97: 148–155.

    Article  CAS  PubMed  Google Scholar 

  34. Cao, W.J., W. Zhang, J.J. Liu, et al. 2011. Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-alpha and IL-1 beta release and augmentation of IL-10 production. International Immunopharmacology 11: 172–178.

    Article  CAS  PubMed  Google Scholar 

  35. Hopkins, S.J. 2003. The pathophysiological role of cytokines. Legal Medicine 5(Suppl 1): S45–S57.

    Article  CAS  PubMed  Google Scholar 

  36. Wang, G., B. Sun, Y. Gao, Q.H. Meng, and H.C. Jiang. 2007. The effect of emodin-assisted early enteral nutrition on severe acute pancreatitis and secondary hepatic injury. Mediators of Inflammation 2007: 29638.

    PubMed  PubMed Central  Google Scholar 

  37. Noreen, M., and M. Arshad. 2015. Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility. Immunologic Research 62: 234–252.

    Article  CAS  PubMed  Google Scholar 

  38. Takeuchi, O., K. Hoshino, T. Kawai, et al. 1999. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11: 443–451.

    Article  CAS  PubMed  Google Scholar 

  39. Xiang, P., T. Chen, Y. Mou, et al. 2015. NZ suppresses TLR4/NF-kappaB signalings and NLRP3 inflammasome activation in LPS-induced RAW264.7 macrophages. Inflammation Research 64: 799–808.

    Article  CAS  PubMed  Google Scholar 

  40. Yamamoto, Y., and R.B. Gaynor. 2004. IkappaB kinases: key regulators of the NF-kappaB pathway. Trends in Biochemical Sciences 29: 72–79.

    Article  CAS  PubMed  Google Scholar 

  41. Ren, J., and S.H. Chung. 2007. Anti-inflammatory effect of alpha-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-kappaB and mitogen-activated protein kinase pathways. Journal of Agricultural and Food Chemistry 55: 5073–5080.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Foundation of China (NO.31272631, 31472254).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ganzhen Deng.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Additional information

Haichong Wu and Gan Zhao 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

Wu, H., Zhao, G., Jiang, K. et al. IFN-τ Alleviates Lipopolysaccharide-Induced Inflammation by Suppressing NF-κB and MAPKs Pathway Activation in Mice. Inflammation 39, 1141–1150 (2016). https://doi.org/10.1007/s10753-016-0348-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-016-0348-9

KEY WORDS

Navigation