DOI QR코드

DOI QR Code

Lactoferrin Stimulates Mouse Macrophage to Express BAFF via Smad3 Pathway

  • Chang, Heyn-Keyung (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Jin, Bo-Ra (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Jang, Young-Saeng (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University) ;
  • Kim, Woan-Sub (Division of Animal Life and Environmental Science, College of Agriculture and Life Science, Hankyong National University) ;
  • Kim, Pyeung-Hyeun (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University)
  • Received : 2012.04.18
  • Accepted : 2012.05.18
  • Published : 2012.06.30

Abstract

B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and stimulates B cell proliferation, differentiation, survival, and Ig production. In this study, we explored the effect of lactoferrin (LF) on BAFF expression by murine macrophages. We determined the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA, respectively. LF markedly enhanced BAFF expression in mouse macrophages at both the transcriptional and protein levels. Overexpression of Smad3/4 further increased LF-induced BAFF transcription while DN-Smad3 abolished the LF-induced BAFF expression. These results demonstrate that LF can enhance BAFF expression through Smad3/4 pathway.

Keywords

References

  1. Metz-Boutigue, M. H., J. Jolles, J. Mazurier, F. Schoentgen, D. Legrand, G. Spik, J. Montreuil, and P. Jolles. 1984. Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins. Eur. J. Biochem. 145: 659-676. https://doi.org/10.1111/j.1432-1033.1984.tb08607.x
  2. Legrand, D., E. Elass, M. Carpentier, and J. Mazurier. 2005. Lactoferrin: a modulator of immune and inflammatory responses. Cell Mol. Life Sci. 62: 2549-2559. https://doi.org/10.1007/s00018-005-5370-2
  3. Valenti, P., and G. Antonini. 2005. Lactoferrin: an important host defence against microbial and viral attack. Cell Mol. Life Sci. 62: 2576-2587. https://doi.org/10.1007/s00018-005-5372-0
  4. Puddu, P., P. Valenti, and S. Gessani. 2009. Immunomodulatory effects of lactoferrin on antigen presenting cells. Biochimie. 91: 11-18. https://doi.org/10.1016/j.biochi.2008.05.005
  5. Puddu, P., D. Latorre, M. Carollo, A. Catizone, G. Ricci, P. Valenti, and S. Gessani. 2011. Bovine lactoferrin counteracts Toll-like receptor mediated activation signals in antigen presenting cells. PLoS One 6: e22504. https://doi.org/10.1371/journal.pone.0022504
  6. Craxton, A., D. Magaletti, E. J. Ryan, and E. A. Clark. 2003. Macrophage- and dendritic cell--dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF. Blood 101: 4464-4471. https://doi.org/10.1182/blood-2002-10-3123
  7. Dubois, B., B. Vanbervliet, J. Fayette, C. Massacrier, C. Van Kooten, F. Briere, J. Banchereau, and C. Caux. 1997. Dendritic cells enhance growth and differentiation of CD40- activated B lymphocytes. J. Exp. Med. 185: 941-951. https://doi.org/10.1084/jem.185.5.941
  8. Fagarasan, S., and T. Honjo. 2000. T-Independent immune response: new aspects of B cell biology. Science 290: 89-92. https://doi.org/10.1126/science.290.5489.89
  9. Groom, J., S. L. Kalled, A. H. Cutler, C. Olson, S. A. Woodcock, P. Schneider, J. Tschopp, T. G. Cachero, M. Batten, J. Wheway, D. Mauri, D. Cavill, T. P. Gordon, C. R. Mackay, and F. Mackay. 2002. Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome. J. Clin. Invest. 109: 59-68. https://doi.org/10.1172/JCI0214121
  10. Mackay, F., and C. Ambrose. 2003. The TNF family members BAFF and APRIL: the growing complexity. Cytokine Growth Factor Rev. 14: 311-324. https://doi.org/10.1016/S1359-6101(03)00023-6
  11. Sutherland, A. P., F. Mackay, and C. R. Mackay. 2006. Targeting BAFF: immunomodulation for autoimmune diseases and lymphomas. Pharmacol. Ther. 112: 774-786. https://doi.org/10.1016/j.pharmthera.2006.06.002
  12. Park, S. R., J. H. Lee, and P. H. Kim. 2001. Smad3 and Smad4 mediate transforming growth factor-beta1-induced IgA expression in murine B lymphocytes. Eur. J. Immunol. 31: 1706-1715. https://doi.org/10.1002/1521-4141(200106)31:6<1706::AID-IMMU1706>3.0.CO;2-Z
  13. Imamura, T., M. Takase, A. Nishihara, E. Oeda, J. Hanai, M. Kawabata, and K. Miyazono. 1997. Smad6 inhibits signalling by the TGF-beta superfamily. Nature 389: 622-626. https://doi.org/10.1038/39355
  14. Goto, D., K. Yagi, H. Inoue, I. Iwamoto, M. Kawabata, K. Miyazono, and M. Kato. 1998. A single missense mutant of Smad3 inhibits activation of both Smad2 and Smad3, and has a dominant negative effect on TGF-beta signals. FEBS Lett. 430: 201-204. https://doi.org/10.1016/S0014-5793(98)00658-9
  15. Kim, H. A., S. H. Jeon, G. Y. Seo, J. B. Park, and P. H. Kim. 2008. TGF-beta1 and IFN-gamma stimulate mouse macrophages to express BAFF via different signaling pathways. J. Leukoc. Biol. 83: 1431-1439. https://doi.org/10.1189/jlb.1007676
  16. Zemann, N., P. Klein, E. Wetzel, F. Huettinger, and M. Huettinger. 2010. Lactoferrin induces growth arrest and nuclear accumulation of Smad-2 in HeLa cells. Biochimie. 92: 880-884. https://doi.org/10.1016/j.biochi.2010.03.013

Cited by

  1. Silk peptide treatment potentiates natural killer cell activity in vitro and induces natural killer cell maturation and activation in mouse splenocytes vol.57, pp.1, 2019, https://doi.org/10.1080/13880209.2019.1617749
  2. RIG-I-like receptors direct inflammatory macrophage polarization against West Nile virus infection vol.10, pp.1, 2012, https://doi.org/10.1038/s41467-019-11250-5