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Inflammation Research

, Volume 60, Issue 9, pp 807–815 | Cite as

BAFF and APRIL induce inflammatory activation of THP-1 cells through interaction with their conventional receptors and activation of MAPK and NF-κB

  • Sang-Min Lee
  • Eun-Ju Kim
  • Kyoungho Suk
  • Won-Ha Lee
Original Research Paper

Abstract

Background

BAFF and APRIL, as closely related members of the TNF superfamily, are important regulators of B-cell survival. They share two receptors, TACI and BCMA, and BAFF can stimulate an additional receptor, BAFF-R. Although these molecules have been under intense investigation in order to identify their role in immune reactions, the effect of BAFF and APRIL on macrophage function has not been tested.

Methods

The human macrophage-like cell line THP-1, which expresses BAFF/APRIL and all three of their receptors, was stimulated with recombinant human BAFF or APRIL or monoclonal antibodies against the receptors and the resulting cellular responses were investigated. Treatment of the cells with these agents induced the expression of pro-inflammatory mediators such as matrix metalloproteinase (MMP)-9 and IL-8. Suppression of the expression of these receptors using specific siRNAs resulted in the blocking of the response, confirming that these responses require specific interaction between BAFF/APRIL and their receptors. Inhibitors of MAPK and NF-κB blocked the expression of IL-8. Furthermore, inhibitors of MAPK blocked the BAFF-induced specific DNA binding activity of NF-κB.

Conclusion

These data indicate that BAFF and APRIL can induce inflammatory activation of THP-1 cells through the activation of MAPK, which leads to the subsequent activation of NF-κB.

Keywords

BAFF APRIL MAPK NF-κB Inflammation 

Notes

Acknowledgments

This work was supported by a grant provided by the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/Anti-aging and Well-being Research Center).

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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • Sang-Min Lee
    • 1
  • Eun-Ju Kim
    • 1
  • Kyoungho Suk
    • 2
  • Won-Ha Lee
    • 1
  1. 1.School of Life Sciences and BiotechnologyKyungpook National UniversityDaeguKorea
  2. 2.Department of Pharmacology, Brain Science and Engineering Institute, School of MedicineKyungpook National UniversityDaeguKorea

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