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Brain-Derived Neurotrophic Factor Inhibits Intercellular Adhesion Molecule-1 Expression in Interleukin-1β-Treated Endothelial Cells

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Abstract

Brain-derived neurotrophic factor (BDNF) enhances periodontal tissue regeneration. Tissue regeneration is characterized by inflammation, which directs the quality of tissue repair. The objective of this study is to propose the relevance of BDNF to inflammation. In this study, we investigated the effect of BDNF on intercellular adhesion molecule (ICAM)-1, which is an inflammatory marker, expressed in interleukin (IL)-1β-treated human microvascular endothelial cells (HMVECs). In addition, we studied the effect of BDNF on the adhesion of neutrophil-like differentiated HL-60 cells to HMVECs in a cell adhesion assay. We demonstrated that BDNF attenuates the IL-1β-induced ICAM-1 mRNA and protein expression. Treatment of HMVECs with IL-1β led to an increase in the number of adherent neutrophil-like HL-60 cells. BDNF significantly decreased the number of neutrophil-like HL-60 cells attached to HMVECs. In conclusion, BDNF may reduce excess inflammation through reduced neutrophil recruitment by regulating ICAM-1 expression.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

ICAM-1:

Intercellular adhesion molecule-1

HMVECs:

Human microvascular endothelial cells

References

  1. Aukhil, I. (2000). Biology of wound healing. Periodontol, 22, 44–50.

    Article  CAS  Google Scholar 

  2. Eming, S. A., Krieg, T., & Davidson, J. M. (2007). Inflammation in wound repair: Molecular and cellular mechanisms. Journal of Investigative Dermatology, 127, 514–525.

    Article  CAS  PubMed  Google Scholar 

  3. Liu, Y. C., Lerner, U. H., & Teng, Y. T. (2000). Cytokine responses against periodontal infection: Protective and destructive roles. Periodontol, 2010(52), 163–206.

    Google Scholar 

  4. Eming, S. A., Hammerschmidt, M., Krieg, T., & Roers, A. (2009). Interrelation of immunity and tissue repair or regeneration. Seminars in Cell & Developmental Biology, 20, 517–527.

    Article  CAS  Google Scholar 

  5. Barbacid, M. (1994). The trk family of neurotrophin receptors. Journal of Neurobiology, 25, 1386–1403.

    Article  CAS  PubMed  Google Scholar 

  6. Ebendal, T. (1992). Function and evolution in the ngf family and its receptors. Journal of Neuroscience Research, 32, 461–470.

    Article  CAS  PubMed  Google Scholar 

  7. Johnson, D., Lanahan, A., Buck, C. R., Sehgal, A., Morgan, C., Mercer, E., et al. (1986). Expression and structure of the human ngf receptor. Cell, 47, 545–554.

    Article  CAS  PubMed  Google Scholar 

  8. Radeke, M. J., Misko, T. P., Hsu, C., Herzenberg, L. A., & Shooter, E. M. (1987). Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature, 325, 593–597.

    Article  CAS  PubMed  Google Scholar 

  9. Patapoutian, A., & Reichardt, L. F. (2001). Trk receptors: Mediators of neurotrophin action. Current Opinion in Neurobiology, 11, 272–280.

    Article  CAS  PubMed  Google Scholar 

  10. Kajiya, M., Shiba, H., Fujita, T., Ouhara, K., Takeda, K., Mizuno, N., et al. (2008). Brain-derived neurotrophic factor stimulates bone/cementum-related protein gene expression in cementoblasts. Journal of Biological Chemistry, 283, 16259–16267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kajiya, M., Shiba, H., Fujita, T., Takeda, K., Uchida, Y., Kawaguchi, H., et al. (2009). Brain-derived neurotrophic factor protects cementoblasts from serum starvation-induced cell death. Journal of Cellular Physiology, 221, 696–706.

    Article  CAS  PubMed  Google Scholar 

  12. Kerschensteiner, M., Gallmeier, E., Behrens, L., Leal, V. V., Misgeld, T., Klinkert, W. E., et al. (1999). Activated human t cells, b cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation? Journal of Experimental Medicine, 189, 865–870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nakahashi, T., Fujimura, H., Altar, C. A., Li, J., Kambayashi, J., Tandon, N. N., & Sun, B. (2000). Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS Letters, 470, 113–117.

    Article  CAS  PubMed  Google Scholar 

  14. Nakanishi, T., Takahashi, K., Aoki, C., Nishikawa, K., Hattori, T., & Taniguchi, S. (1994). Expression of nerve growth factor family neurotrophins in a mouse osteoblastic cell line. Biochemical and biophysical research communications, 198, 891–897.

    Article  CAS  PubMed  Google Scholar 

  15. Takeda, K., Shiba, H., Mizuno, N., Hasegawa, N., Mouri, Y., Hirachi, A., et al. (2005). Brain-derived neurotrophic factor enhances periodontal tissue regeneration. Tissue Engineering, 11, 1618–1629.

    Article  CAS  PubMed  Google Scholar 

  16. Takeda, K., Sakai, N., Shiba, H., Nagahara, T., Fujita, T., Kajiya, M., et al. (2011). Characteristics of high-molecular-weight hyaluronic acid as a brain-derived neurotrophic factor scaffold in periodontal tissue regeneration. Tissue Engineering Part A, 17, 955–967.

    Article  CAS  PubMed  Google Scholar 

  17. Dinarello, C. A. (2002). The il-1 family and inflammatory diseases. Clinical and Experimental Rheumatology, 20, S1–S13.

    CAS  Google Scholar 

  18. Graves, D. T., & Cochran, D. (2003). The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. Journal of Periodontology, 74, 391–401.

    Article  CAS  PubMed  Google Scholar 

  19. Firestein, G. S. (2003). Evolving concepts of rheumatoid arthritis. Nature, 423, 356–361.

    Article  CAS  PubMed  Google Scholar 

  20. Kornman, K. S., Page, R. C., & Tonetti, M. S. (2000). The host response to the microbial challenge in periodontitis: Assembling the players. Periodontol, 1997(14), 33–53.

    Google Scholar 

  21. Labus, J., Hackel, S., Lucka, L., & Danker, K. (2014). Interleukin-1beta induces an inflammatory response and the breakdown of the endothelial cell layer in an improved human thbmec-based in vitro blood-brain barrier model. Journal of Neuroscience Methods, 228, 35–45.

    Article  CAS  PubMed  Google Scholar 

  22. Berendji-Grun, D., Kolb-Bachofen, V., & Kroncke, K. D. (2001). Nitric oxide inhibits endothelial il-1[beta]-induced icam-1 gene expression at the transcriptional level decreasing sp1 and ap-1 activity. Molecular Medicine, 7, 748–754.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Williams, M. R., Azcutia, V., Newton, G., Alcaide, P., & Luscinskas, F. W. (2011). Emerging mechanisms of neutrophil recruitment across endothelium. Trends in Immunology, 32, 461–469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wu, T., McGrath, K. C., & Death, A. K. (2005). Cardiovascular disease in diabetic nephropathy patients: Cell adhesion molecules as potential markers? Vascular Health and Risk Management, 1, 309–316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Matsuda, S., Fujita, T., Kajiya, M., Takeda, K., Shiba, H., Kawaguchi, H., & Kurihara, H. (2012). Brain-derived neurotrophic factor induces migration of endothelial cells through a trkb-erk-integrin alphavbeta3-fak cascade. Journal of Cellular Physiology, 227, 2123–2129.

    Article  CAS  PubMed  Google Scholar 

  26. Ley, K., Laudanna, C., Cybulsky, M. I., & Nourshargh, S. (2007). Getting to the site of inflammation: The leukocyte adhesion cascade updated. Nature Reviews Immunology, 7, 678–689.

    Article  CAS  PubMed  Google Scholar 

  27. Petri, B., Phillipson, M., & Kubes, P. (2008). The physiology of leukocyte recruitment: An in vivo perspective. Journal of Immunology, 180, 6439–6446.

    Article  CAS  Google Scholar 

  28. Wong, C. H., Heit, B., & Kubes, P. (2010). Molecular regulators of leucocyte chemotaxis during inflammation. Cardiovascular Research, 86, 183–191.

    Article  CAS  PubMed  Google Scholar 

  29. Zarbock, A., & Ley, K. (2009). Neutrophil adhesion and activation under flow. Microcirculation, 16, 31–42.

    Article  CAS  PubMed  Google Scholar 

  30. Hossain, M., Qadri, S. M., Su, Y., & Liu, L. (2013). Icam-1-mediated leukocyte adhesion is critical for the activation of endothelial lsp1. American Journal of Physiology-Cell Physiology, 304, C895–C904.

    Article  CAS  PubMed  Google Scholar 

  31. Abram, C. L., & Lowell, C. A. (2009). The ins and outs of leukocyte integrin signaling. Annual Review of Immunology, 27, 339–362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Katagiri, K., & Kinashi, T. (2012). Rap1 and integrin inside-out signaling. Methods in Molecular Biology, 757, 279–296.

    Article  PubMed  Google Scholar 

  33. Takeda, K., Kermani, P., Anastasia, A., Obinata, Y., Hempstead, B. L., & Kurihara, H. (2013). Bdnf protects human vascular endothelial cells from tnfalpha-induced apoptosis. Biochemistry and Cell Biology, 91, 341–349.

    Article  CAS  PubMed  Google Scholar 

  34. Butcher, E. C. (1991). Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity. Cell, 67, 1033–1036.

    Article  CAS  PubMed  Google Scholar 

  35. Springer, T. A. (1994). Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell, 76, 301–314.

    Article  CAS  PubMed  Google Scholar 

  36. Nguyen, D. K., Montesinos, M. C., Williams, A. J., Kelly, M., & Cronstein, B. N. (2003). Th1 cytokines regulate adenosine receptors and their downstream signaling elements in human microvascular endothelial cells. Journal of Immunology, 171, 3991–3998.

    Article  Google Scholar 

  37. Donovan, M. J., Lin, M. I., Wiegn, P., Ringstedt, T., Kraemer, R., Hahn, R., et al. (2000). Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. Development, 127, 4531–4540.

    CAS  PubMed  Google Scholar 

  38. Kermani, P., & Hempstead, B. (2007). Brain-derived neurotrophic factor: A newly described mediator of angiogenesis. Trends in Cardiovascular Medicine, 17, 140–143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (C) (No. 25463218) from the Japan Society for the Promotion of Science, Japan. Katsuhiro Takeda has received a Grant-in-Aid for Scientific Research (C) (No. 25463218) from the Japan Society for the Promotion of Science, Japan.

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Authors and Affiliations

  1. Division of Applied Life Sciences, Department of Periodontal Medicine, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan

    Katsuhiro Takeda, Yusuke Obinata, Akihiro Konishi, Mikihito Kajiya, Shinji Matsuda, Noriyoshi Mizuno, Shinya Sasaki, Tsuyoshi Fujita & Hidemi Kurihara

  2. Division of Frontier Medical Science, Department of Periodontal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Katsuhiro Takeda

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  1. Katsuhiro Takeda
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  2. Yusuke Obinata
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Correspondence to Katsuhiro Takeda.

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Yusuke Obinata, Akihiro Konishi, Mikihito Kajiya, Shinji Matsuda, Noriyoshi Mizuno, Tsuyoshi Fujita and Hidemi Kurihara declare that they have no conflict of interest.

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Takeda, K., Obinata, Y., Konishi, A. et al. Brain-Derived Neurotrophic Factor Inhibits Intercellular Adhesion Molecule-1 Expression in Interleukin-1β-Treated Endothelial Cells. Cell Biochem Biophys 74, 399–406 (2016). https://doi.org/10.1007/s12013-016-0749-2

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