Rapid induction of peroxisome proliferator–activated receptor γ expression in human monocytes by monosodium urate monohydrate crystals
Article first published online: 10 JAN 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 1, pages 231–239, January 2003
How to Cite
Akahoshi, T., Namai, R., Murakami, Y., Watanabe, M., Matsui, T., Nishimura, A., Kitasato, H., Kameya, T. and Kondo, H. (2003), Rapid induction of peroxisome proliferator–activated receptor γ expression in human monocytes by monosodium urate monohydrate crystals. Arthritis & Rheumatism, 48: 231–239. doi: 10.1002/art.10709
- Issue published online: 10 JAN 2003
- Article first published online: 10 JAN 2003
- Manuscript Accepted: 11 SEP 2002
- Manuscript Received: 8 JAN 2002
- Ministry of Health, Labor, and Welfare of Japan
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
Peroxisome proliferator–activated receptor γ (PPARγ) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPARγ in self-limiting episodes of acute gouty arthritis. To do this, we investigated PPARγ expression by monosodium urate monohydrate (MSU) crystal–stimulated monocytes, and we studied the effects of PPARγ ligands on crystal-induced acute inflammation.
PPARγ expression by MSU crystal–stimulated human peripheral blood mononuclear cells was determined by reverse transcription–polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPARγ ligands on in vitro crystal-induced cytokine production and on in vivo cellular infiltration during crystal-induced acute inflammation were also investigated.
MSU crystals rapidly and selectively induced PPARγ expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPARγ was functional, since a PPARγ ligand was able to up-regulate CD36 expression on monocytes. A natural ligand of PPARγ, 15-deoxy-Δ12,14-prostaglandin J2 (15deoxy-PGJ2), significantly reduced the crystal-induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy-PGJ2 significantly prevented cellular accumulation in a mouse air-pouch model of MSU crystal–induced acute inflammation.
Rapid induction of PPARγ expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout.