Redox Factor-1 Inhibits Cyclooxygenase-2 Expression via Inhibiting of p38 MAPK in the A549 Cells
The Korean Journal of Physiology and Pharmacology
;
: 139-144, 2010.
Article
in English
| WPRIM
| ID: wpr-727808
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oxidation-Reduction
/
Phosphorylation
/
Pyridines
/
Transfection
/
Adenocarcinoma
/
Gene Expression
/
Cell Line
/
Tumor Necrosis Factor-alpha
/
P38 Mitogen-Activated Protein Kinases
/
Cyclooxygenase 2
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2010
Type:
Article
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