Triptolide suppresses interleukin-1β-induced human β-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-κB in A549 cells

  • Authors:
    • Byeong-Churl Jang
    • Ki-Jo Lim
    • In-Hak Choi
    • Min-Ho Suh
    • Jong-Gu Park
    • Kyo-Chul Mun
    • Jae-Hoon Bae
    • Dong-Hoon Shin
    • Seong-Il Suh
  • View Affiliations

  • Published online on: May 1, 2007     https://doi.org/10.3892/ijmm.19.5.757
  • Pages: 757-763
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Abstract

The immunosuppressive effect of triptolide has been associated with suppression of T-cell activation. However, the immunosuppressive effects of triptolide on innate immunity in the epithelial barrier remain to be elucidated. Human β-defensin (HBD)-2 is an inducible antimicrobial peptide and plays an important role in the innate immunity. We have previously demonstrated that IL-1β induced HBD-2 mRNA expression in A549 cells through activation of nuclear factor-κB (NF-κB) transcriptional factor as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase (PI3K). In this study, we investigated effects of triptolide on IL-1β-induced HBD-2 mRNA expression in A549 cells. Triptolide inhibited IL-1β-induced HBD-2 mRNA expression in a dose-dependent manner. Addition of triptolide did not suppress activation of p38 MAPK, JNK, or PI3K in response to IL-1β. Triptolide inhibited IL-1β-induced MAPK phosphatase-1 expression at the transcriptional level and resulted in sustained phosphorylation of JNK or p38 MAPK, explaining the little effect of triptolide on IL-1β-induced phosphorylation of these kinases. Although triptolide partially suppressed IL-1β-mediated degradation of IκB-α and nuclear translocation of p65 NF-κB, triptolide potently inhibited NF-κB promoter-driven luciferase activity in A549 cells. These results collectively suggest that the inhibitory effect of triptolide on IL-1β-induced HBD-2 mRNA expression in A549 cells seems to be at least in part mediated through nuclear inhibition of NF-κB transcriptional activity, but not inhibition of p38 MAPK, JNK, or PI3K. This inhibition may explain the ability of triptolide to diminish innate immune response.

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May 2007
Volume 19 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Jang B, Lim K, Choi I, Suh M, Park J, Mun K, Bae J, Shin D and Suh S: Triptolide suppresses interleukin-1β-induced human β-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-κB in A549 cells. Int J Mol Med 19: 757-763, 2007
APA
Jang, B., Lim, K., Choi, I., Suh, M., Park, J., Mun, K. ... Suh, S. (2007). Triptolide suppresses interleukin-1β-induced human β-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-κB in A549 cells. International Journal of Molecular Medicine, 19, 757-763. https://doi.org/10.3892/ijmm.19.5.757
MLA
Jang, B., Lim, K., Choi, I., Suh, M., Park, J., Mun, K., Bae, J., Shin, D., Suh, S."Triptolide suppresses interleukin-1β-induced human β-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-κB in A549 cells". International Journal of Molecular Medicine 19.5 (2007): 757-763.
Chicago
Jang, B., Lim, K., Choi, I., Suh, M., Park, J., Mun, K., Bae, J., Shin, D., Suh, S."Triptolide suppresses interleukin-1β-induced human β-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-κB in A549 cells". International Journal of Molecular Medicine 19, no. 5 (2007): 757-763. https://doi.org/10.3892/ijmm.19.5.757