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Article

Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity

  • Authors:
    • Hua Hong
    • Byeong-Churl Jang
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Medicine, College of Medicine, Keimyung University, Dalseo-gu, Daegu 704-701, Republic of Korea
  • Pages: 1640-1646
    |
    Published online on: October 14, 2014
       https://doi.org/10.3892/ijmm.2014.1967
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Abstract

Hearing loss can be induced by multiple causes, including cochlear inflammation. Prednisone (PDN) is a well‑known steroid clinically used in the treatment of hearing loss. In the present study, we investigated the inhibitory effects and the mechanisms of action of PDN on the expression of cyclooxygenase (COX)-2, an inflammatory enzyme involved in the production of prostaglandins (PGs), in House Ear Institute-Organ of Corti 1 (HEI‑OC1) cells (a murine auditory cell line) treated with the inflammatory cytokine, interleukin (IL)-1β. The exposure of HEI-OC1 cells to IL-1β increased COX-2 protein and mRNA expression, COX-2 promoter-driven luciferase activity and COX-2 enzymatic activity [as indicated by the increased production of prostaglandin E2 (PGE2), a major COX-2 metabolite]. However, PDN markedly inhibited the IL-1β-induced COX-2 protein and mRNA expression, COX-2 promoter activity and PGE2 production in the HEI-OC1 cells without affecting COX-2 protein and mRNA stability. PDN further inhibited the IL-1β-induced activation of extracellular signal-regulated kinase (ERK)-1/2 and c-Jun N-terminal kinase (JNK)-1, but had no effect on the cytokine‑induced activation of p38 MAPK and proteolysis of IκB-α, a nuclear factor-κB (NF-κB) inhibitory protein. PDN also partially suppressed the IL-1β‑induced activation of activator protein (AP)-1 (but not that of NF-κB) promoter-driven luciferase activity. Of note, the inhibitory effects of PDN on the IL-1β-induced expression of COX-2 and the activation of ERK-1/2 and JNK-1 in the HEI-OC1 cells were significantly diminished by RU486, a glucocorticoid receptor (GR) antagonist, suggesting that PDN exerts its inhibitory effects through GR. To the best of our knowledge, our study demonstrates for the first time that PDN inhibits the IL-1β-induced COX-2 expression and activity in HEI-OC1 cells by COX-2 transcriptional repression, which is partly associated with the inhibition of ERK-1/2, JNK-1 and AP-1 activation.
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Copy and paste a formatted citation
Spandidos Publications style
Hong H and Jang B: Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity. Int J Mol Med 34: 1640-1646, 2014.
APA
Hong, H., & Jang, B. (2014). Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity. International Journal of Molecular Medicine, 34, 1640-1646. https://doi.org/10.3892/ijmm.2014.1967
MLA
Hong, H., Jang, B."Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity". International Journal of Molecular Medicine 34.6 (2014): 1640-1646.
Chicago
Hong, H., Jang, B."Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity". International Journal of Molecular Medicine 34, no. 6 (2014): 1640-1646. https://doi.org/10.3892/ijmm.2014.1967
Copy and paste a formatted citation
x
Spandidos Publications style
Hong H and Jang B: Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity. Int J Mol Med 34: 1640-1646, 2014.
APA
Hong, H., & Jang, B. (2014). Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity. International Journal of Molecular Medicine, 34, 1640-1646. https://doi.org/10.3892/ijmm.2014.1967
MLA
Hong, H., Jang, B."Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity". International Journal of Molecular Medicine 34.6 (2014): 1640-1646.
Chicago
Hong, H., Jang, B."Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity". International Journal of Molecular Medicine 34, no. 6 (2014): 1640-1646. https://doi.org/10.3892/ijmm.2014.1967
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