15d-PGJ2 inhibits oxidized LDL-induced macrophage proliferation by inhibition of GM-CSF production via inactivation of NF-κB

Tomoko Matsuo, Takeshi Matsumura, Masakazu Sakai, Takafumi Senokuchi, Miyuki Yano, Shinsuke Kiritoshi, Kazuhiro Sonoda, Daisuke Kukidome, Richard G. Pestell, Michael Brownlee, Takeshi Nishikawa, Eiichi Araki

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)817-823
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume314
Issue number3
DOIs
StatePublished - Feb 13 2004

Fingerprint

Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Peritoneal Macrophages
Thymidine
Genes
Peroxisome Proliferator-Activated Receptors
Foam Cells
15-deoxy-delta(12,14)-prostaglandin J2
oxidized low density lipoprotein
Foams
Reporter Genes
Assays
Ligands
Messenger RNA
cyclopentenone

Keywords

  • 15-Deoxy-Δ-prostaglandin J
  • Atherosclerosis
  • Granulocyte/macrophage colony stimulating factor
  • Macrophage proliferation
  • Oxidized low-density lipoprotein

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

15d-PGJ2 inhibits oxidized LDL-induced macrophage proliferation by inhibition of GM-CSF production via inactivation of NF-κB. / Matsuo, Tomoko; Matsumura, Takeshi; Sakai, Masakazu; Senokuchi, Takafumi; Yano, Miyuki; Kiritoshi, Shinsuke; Sonoda, Kazuhiro; Kukidome, Daisuke; Pestell, Richard G.; Brownlee, Michael; Nishikawa, Takeshi; Araki, Eiichi.

In: Biochemical and Biophysical Research Communications, Vol. 314, No. 3, 13.02.2004, p. 817-823.

Research output: Contribution to journalArticle

Matsuo, T, Matsumura, T, Sakai, M, Senokuchi, T, Yano, M, Kiritoshi, S, Sonoda, K, Kukidome, D, Pestell, RG, Brownlee, M, Nishikawa, T & Araki, E 2004, '15d-PGJ2 inhibits oxidized LDL-induced macrophage proliferation by inhibition of GM-CSF production via inactivation of NF-κB', Biochemical and Biophysical Research Communications, vol. 314, no. 3, pp. 817-823. https://doi.org/10.1016/j.bbrc.2003.12.161
Matsuo, Tomoko ; Matsumura, Takeshi ; Sakai, Masakazu ; Senokuchi, Takafumi ; Yano, Miyuki ; Kiritoshi, Shinsuke ; Sonoda, Kazuhiro ; Kukidome, Daisuke ; Pestell, Richard G. ; Brownlee, Michael ; Nishikawa, Takeshi ; Araki, Eiichi. / 15d-PGJ2 inhibits oxidized LDL-induced macrophage proliferation by inhibition of GM-CSF production via inactivation of NF-κB. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 314, No. 3. pp. 817-823.
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