계명대학교 의학도서관 Repository

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

Metadata Downloads
Author(s)
HUA HONGBYEONG-CHURL JANG
Keimyung Author(s)
Jang, Byeong Churl
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
International Journal of Molecular Medicine
Issued Date
2014
Volume
34
Issue
6
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.
Keimyung Author(s)(Kor)
장병철
Publisher
School of Medicine
Citation
HUA HONG and BYEONG-CHURL JANG. (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(6), 1640–1646. doi: 10.3892/ijmm.2014.1967
Type
Article
ISSN
1107-3756
Source
https://www.spandidos-publications.com/ijmm/34/6/1640
DOI
10.3892/ijmm.2014.1967
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35917
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
공개 및 라이선스
  • 공개 구분공개
  • 엠바고Forever
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.