title: Redox Factor-1 Inhibits Cyclooxygenase-2 Expression via Inhibiting of p38 MAPK in the A549 Cells.
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 (Adbetagal). Pretreatment with 10 microM 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.
authors.affiliation: Department of Physiology, Infection Signaling Network Research Center, and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, Daejeon 301-131, Korea.
authors.forename: Dae Goon
authors.initials: DG
authors.lastname: Yoo
authors.forename: Cuk Seong
authors.initials: CS
authors.lastname: Kim
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Lee
authors.forename: Hyo Shin
authors.initials: HS
authors.lastname: Kim
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Cho
authors.forename: Myoung Soo
authors.initials: MS
authors.lastname: Park
authors.forename: Sang Do
authors.initials: SD
authors.lastname: Lee
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon