TY - JOUR
T1 - 15d-PGJ2 inhibits oxidized LDL-induced macrophage proliferation by inhibition of GM-CSF production via inactivation of NF-κB
AU - Matsuo, Tomoko
AU - Matsumura, Takeshi
AU - Sakai, Masakazu
AU - Senokuchi, Takafumi
AU - Yano, Miyuki
AU - Kiritoshi, Shinsuke
AU - Sonoda, Kazuhiro
AU - Kukidome, Daisuke
AU - Pestell, Richard G.
AU - Brownlee, Michael
AU - Nishikawa, Takeshi
AU - Araki, Eiichi
PY - 2004/2/13
Y1 - 2004/2/13
N2 - Macrophage-derived foam cells play an important role in atherosclerotic lesions. Oxidized low-density lipoprotein (Ox-LDL) induces macrophage proliferation via production of GM-CSF in vitro. This study investigated the effects of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand for peroxisome proliferator-activated receptor γ, on macrophage proliferation. Mouse peritoneal macrophages and RAW264.7 cells were used for proliferation study and reporter gene assay, respectively. Twenty microgram per milliliter of Ox-LDL induced [ 3H]thymidine incorporation in mouse peritoneal macrophages, and 15d-PGJ2 inhibited Ox-LDL-induced [3H]thymidine incorporation in a dose-dependent manner. Ox-LDL increased GM-CSF release and GM-CSF mRNA expression, and activated GM-CSF gene promoter, all of which were prevented by 15d-PGJ2 or 2-cyclopenten-1-one, a cyclopentenone ring of 15d-PGJ2. The suppression of GM-CSF promoter activity by 15d-PGJ2 and 2-cyclopenten-1-one was mediated through reduction of NF-κB binding to GM-CSF promoter. These results suggest that 15d-PGJ 2 inhibits Ox-LDL-induced macrophage proliferation through suppression of GM-CSF production via NF-κB inactivation.
AB - Macrophage-derived foam cells play an important role in atherosclerotic lesions. Oxidized low-density lipoprotein (Ox-LDL) induces macrophage proliferation via production of GM-CSF in vitro. This study investigated the effects of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand for peroxisome proliferator-activated receptor γ, on macrophage proliferation. Mouse peritoneal macrophages and RAW264.7 cells were used for proliferation study and reporter gene assay, respectively. Twenty microgram per milliliter of Ox-LDL induced [ 3H]thymidine incorporation in mouse peritoneal macrophages, and 15d-PGJ2 inhibited Ox-LDL-induced [3H]thymidine incorporation in a dose-dependent manner. Ox-LDL increased GM-CSF release and GM-CSF mRNA expression, and activated GM-CSF gene promoter, all of which were prevented by 15d-PGJ2 or 2-cyclopenten-1-one, a cyclopentenone ring of 15d-PGJ2. The suppression of GM-CSF promoter activity by 15d-PGJ2 and 2-cyclopenten-1-one was mediated through reduction of NF-κB binding to GM-CSF promoter. These results suggest that 15d-PGJ 2 inhibits Ox-LDL-induced macrophage proliferation through suppression of GM-CSF production via NF-κB inactivation.
KW - 15-Deoxy-Δ-prostaglandin J
KW - Atherosclerosis
KW - Granulocyte/macrophage colony stimulating factor
KW - Macrophage proliferation
KW - Oxidized low-density lipoprotein
UR - http://www.scopus.com/inward/record.url?scp=12144288716&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12144288716&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2003.12.161
DO - 10.1016/j.bbrc.2003.12.161
M3 - Article
C2 - 14741709
AN - SCOPUS:12144288716
SN - 0006-291X
VL - 314
SP - 817
EP - 823
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -