Redox Factor-1 Inhibits Cyclooxygenase-2 Expression via Inhibiting of p38 MAPK in the A549 Cells.
10.4196/kjpp.2010.14.3.139
- Author:
Dae Goon YOO
1
;
Cuk Seong KIM
;
Sang Ki LEE
;
Hyo Shin KIM
;
Eun Jung CHO
;
Myoung Soo PARK
;
Sang Do LEE
;
Jin Bong PARK
;
Byeong Hwa JEON
Author Information
1. Department of Physiology, Infection Signaling Network Research Center, and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon 301-131, Korea. bhjeon@cnu.ac.kr
- Publication Type:Original Article
- Keywords:
Redox factor-1;
Cyclooxygenase-2;
A549;
Lung cancer;
p38 MAPK
- MeSH:
Adenocarcinoma;
Cell Line;
Cyclooxygenase 2;
Gene Expression;
Imidazoles;
Lung;
Lung Neoplasms;
Oxidation-Reduction;
p38 Mitogen-Activated Protein Kinases;
Phosphorylation;
Pyridines;
Transfection;
Tumor Necrosis Factor-alpha
- From:The Korean Journal of Physiology and Pharmacology
2010;14(3):139-144
- CountryRepublic of Korea
- Language:English
-
Abstract:
In this study, we evaluated the role of apurinic/apyrimidinic endonuclease1/redox factor-1 (Ref-1) on the tumor necrosis factor-alpha (TNF-alpha) induced cyclooxygenase-2 (COX-2) expression using A549 lung adenocarcinoma cells. TNF-alpha induced the expression of COX-2 in A549 cells, but did not induce BEAS-2B expression. The expression of COX-2 in A549 cells was TNF-alpha dose-dependent (5~100 ng/ml). TNF-alpha-stimulated A549 cells evidenced increased Ref-1 expression in a dose-dependent manner. The adenoviral transfection of cells with AdRef-1 inhibited TNF-alpha-induced COX-2 expression relative to that seen in the control cells (Ad beta gal). Pretreatment with 10 micrometer of SB203580 suppressed TNF-alpha-induced COX-2 expression, thereby suggesting that p38 MAPK might be involved in COX-2 expression in A549 cells. The phosphorylation of p38 MAPK was increased significantly after 5 minutes of treatment with TNF-alpha, reaching a maximum level at 10 min which persisted for up to 60 min. However, p38MAPK phosphorylation was markedly suppressed in the Ref-1-overexpressed A549 cells. Taken together, our results appear to indicate that Ref-1 negatively regulates COX-2 expression in response to cytokine stimulation via the inhibition of p38 MAPK phosphorylation. In the lung cancer cell lines, Ref-1 may be involved as an important negative regulator of inflammatory gene expression.
