TY - JOUR
T1 - Effects of COX-2 inhibitors on ROS produced by Chlamydia pneumoniae-primed human promonocytic cells (THP-1)
AU - Mouithys-Mickalad, Ange
AU - Deby-Dupont, Ginette
AU - Dogne, Jean-Michel
AU - de Leval, Xavier
AU - Kohnen, Stephan
AU - Navet, Rachel
AU - Sluse, Francis
AU - Hoebeke, Maryse
AU - Pirotte, Bernard
AU - Lamy, Maurice
PY - 2004/12/24
Y1 - 2004/12/24
N2 - Chronic inflammation through foam cells and macrophages is important in atherosclerosis development, and can be considered as therapeutic targets. Cyclooxygenase and NADPH-oxidase were expressed within atherosclerotic lesions. Reactive oxygen species produced by NADPH oxidase were found to trigger the cyclooxygenase-2 expression. The effects of preferential COX-2 inhibitors on ROS produced by Chlamydia-primed human monocytes (THP-1 cells) were evaluated by fluorescence, chemiluminescence, oxymetry, and EPR spin trapping. Fluorescence assays showed an increased production of ROS with Chlamydia versus cells primed by 10(-8)M PMA. COX-2 inhibitors inhibited in a dose-dependent manner the luminol-enhanced CL while ibuprofen and diclofenac increased the chemiluminescence response. By EPR spin trapping, COX-2 inhibitors, ibuprofen, and diclofenac, exhibited a dose-dependent inhibiting effect (10 and 100muM) on the EPR signal appearance. Our cell model combining EPR, chemiluminescence, and oxymetry appeared relevant to study the modulating effects of preferential COX-2 inhibitors on the cell oxidant activity and chronic inflammatory diseases.
AB - Chronic inflammation through foam cells and macrophages is important in atherosclerosis development, and can be considered as therapeutic targets. Cyclooxygenase and NADPH-oxidase were expressed within atherosclerotic lesions. Reactive oxygen species produced by NADPH oxidase were found to trigger the cyclooxygenase-2 expression. The effects of preferential COX-2 inhibitors on ROS produced by Chlamydia-primed human monocytes (THP-1 cells) were evaluated by fluorescence, chemiluminescence, oxymetry, and EPR spin trapping. Fluorescence assays showed an increased production of ROS with Chlamydia versus cells primed by 10(-8)M PMA. COX-2 inhibitors inhibited in a dose-dependent manner the luminol-enhanced CL while ibuprofen and diclofenac increased the chemiluminescence response. By EPR spin trapping, COX-2 inhibitors, ibuprofen, and diclofenac, exhibited a dose-dependent inhibiting effect (10 and 100muM) on the EPR signal appearance. Our cell model combining EPR, chemiluminescence, and oxymetry appeared relevant to study the modulating effects of preferential COX-2 inhibitors on the cell oxidant activity and chronic inflammatory diseases.
KW - Arteriosclerosis
KW - Cell Differentiation
KW - Cell Line
KW - Chlamydophila pneumoniae
KW - Cyclooxygenase Inhibitors
KW - Dose-Response Relationship, Drug
KW - Free Radicals
KW - Humans
KW - Inflammation
KW - Macrophages
KW - Monocytes
KW - Reactive Oxygen Species
KW - Tetradecanoylphorbol Acetate
U2 - 10.1016/j.bbrc.2004.10.155
DO - 10.1016/j.bbrc.2004.10.155
M3 - Article
C2 - 15555544
SN - 0006-291X
VL - 325
SP - 1122
EP - 1130
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -