Rottlerin induces cyclooxygenase-2 upregulation through an ATF4 and reactive oxygen species-independent pathway in HEI-OC1 cells

Seon Min WooWoo Keun LeeKyoung‑Jin MinDong Eun KimSoon Hyung ParkSung Il NamTaeg Kyu Kwon
Dept. of Otorhinolaryngology (이비인후과학); Dept. of Immunology (면역학)
Issue Date
Molecular Medicine Reports, Vol.14(1) : 845-850, 2016
Hearing loss can be caused by infection, inflammation, loud noise and ototoxic drugs. The induction of cyclooxygenase-2 (COX‑2) expression is an important event during the cellular inflammatory response. The present study investigated the effect of rottlerin on CO-2 mRNA and protein expression in HEI-OC1 cells. Cell viability was determined using an MTT assay. Western blotting was used to examine the expression of COX‑2, endoplasmic reticulum stress-associated transcription factors and activation of the MAPK pathway. ROS was measured using the fluorescent probe 2', 7'-dichlorodihydrofluorescein diacetate. Treatment with the natural protein kinase C δ inhibitor, rottlerin, was shown to increase COX‑2 expression at the protein and mRNA levels in a dose‑dependent manner. Rottlerin was shown to induce increased reactive oxygen species (ROS) generation, however, ROS were not critical for rottlerin‑induced upregulation of COX‑2 expression in HEI‑OC1 cells. In addition, rottlerin was shown to increase the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The pharmacological inhibition of p38MAPK and suppression of activating transcription factor 4 (an ER stress‑associated transcription factor) expression by small interfering RNA inhibited rottlerin-induced COX‑2 upregulation. Furthermore, COX‑2 expression levels were increased further when cells were treated with rottlerin and interleukin‑1β or protein kinase C activator, PMA. In conclusion, the results of the present study demonstrated that rottlerin is a novel inducer of COX‑2 expression and identified the mechanisms involved in this process. Rottlerin may be considered a potential activator of repair and remodeling.
rottlerincyclooxygenase‑2activating transcription factor 4p38 mitogen‑activated protein kinaseHEI‑OC1 cells
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1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
Keimyung Author(s)
김동은; 박순형; 남성일; 권택규
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