BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells

  • Authors:
    • Hua Hong
    • Yu-Kyoung Park
    • Jong-Wook Park
    • Jinho Lee
    • Ji-Eun Hong
    • Gy-Young Park
    • Byeong-Churl Jang
  • View Affiliations

  • Published online on: December 15, 2011     https://doi.org/10.3892/ijmm.2011.863
  • Pages: 454-460
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Abstract

Cyclooxygenase (COX)-2 and its products, including PGE2, are key inflammatory mediators. In this study, we have assessed the pharmacological characteristics of BAI, a 3-aminoindazole derivative and a novel cyclin-dependent kinase (CDK) inhibitor, for regulation of COX-2 expression induced by interleukin (IL)-1β in A549 human airway cells. Treatment with BAI strongly inhibited IL-1β-induced expression of COX-2 at both the protein and mRNA levels. Results of luciferase experiments also revealed that BAI treatment reduced IL-1β-induced COX-2 promoter activity. Distinctly, treatment with BAI did not affect IL-1β-induced phospho­rylation of extracellular signal-regulated protein kinase-1/2 (ERK-1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal protein kinase-1/2 (JNK-1/2) and proteolysis of IκB-α, an inhibitor of nuclear factor (NF)-κB, but inhibited IL-1β-induced phosphorylation of histone H1, a target for phosphorylation by CDKs. siRNA transfection experiments demonstrated that knockdown of CDK2 and CDK4 led to a slight reduction of IL-1β-induced histone H1 phosphorylation but had no effect on IL-1β-induced COX-2 expression. Interestingly, additional cell culture experiments showed the ability of BAI to repress the PMA-induced COX-2 expression in A549 cells and serum-dependent COX-2 expression in NCI-H292 cells, a human laryngeal cell line. Collectively, these results demonstrate firstly that BAI downregulates IL-1β-induced COX-2 expression through transcriptional repression, which appears to be independent of CDK2, CDK4, MAPKs and NF-κB, in A549 cells. It is suggested that BAI may be a potential candidate for treatment of the airway inflammatory diseases where COX-2 overexpression is problematic.

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March 2012
Volume 29 Issue 3

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Spandidos Publications style
Hong H, Park Y, Park J, Lee J, Hong J, Park G and Jang B: BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells. Int J Mol Med 29: 454-460, 2012
APA
Hong, H., Park, Y., Park, J., Lee, J., Hong, J., Park, G., & Jang, B. (2012). BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells. International Journal of Molecular Medicine, 29, 454-460. https://doi.org/10.3892/ijmm.2011.863
MLA
Hong, H., Park, Y., Park, J., Lee, J., Hong, J., Park, G., Jang, B."BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells". International Journal of Molecular Medicine 29.3 (2012): 454-460.
Chicago
Hong, H., Park, Y., Park, J., Lee, J., Hong, J., Park, G., Jang, B."BAI, a 3-aminoindazole derivative, inhibits interleukin-1β-induced expression of cyclooxygenase-2 in A549 human airway cells". International Journal of Molecular Medicine 29, no. 3 (2012): 454-460. https://doi.org/10.3892/ijmm.2011.863