Effect of peroxisome proliferator-activated receptor gamma on thromboxane A(2) and prostaglandin E(2) production in macrophage cell lines.
We studied the effect of peroxisome proliferator-activated receptor gamma (PPARgamma) activation on thromboxane A(2)(TXA(2)) and prostaglandin E(2)(PGE(2)) production in monocyte/macrophage cell lines. In present experiment, we used human peripheral blood monocyte (PBMC), monocyte-cell line THP-1 and mouse macrophage-like cell line RAW264.7. The expression of PPARgamma is reported in PBMC and THP-1. Synthetic PPARgamma ligands (troglitazone or BRL49653) inhibited TXA(2) production and enhanced PGE(2) production of PBMC and THP-1. When treated with 0.5-10 microM of troglitazone, there were no significant changes of TXA(2) and PGE(2) production of RAW264.7 cells, which express very low levels of PPARgamma. When RAW264.7 cells was transfected with PPARgamma expression plasmid and treated with troglitazone, PPARgamma was activated in a dose-dependent manner. In PPARgamma-transfected RAW264.7, TXA(2) production was decreased and PGE(2) production was increased by troglitazone treatment. But it needs high concentration of troglitazone (10 microM) for increasing PGE(2) production. These results suggest that PPARgamma may have negative effect on TXA(2) production, and also have slightly positive effect on PGE(2) production of macrophage.
Yamazaki
T
T
Department of Pharmaceutical Sciences, Tohoku University Hospital, Seiryo-machi, Aoba-ku, Sendai, Japan.
Yokoo
T
T
Tomioka
Y
Y
Suzuki
H
H
Hishinuma
T
T
Mizugaki
M
M
D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D013928:Thromboxane A2 / Q000096:biosynthesis*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D000077288:Troglitazone
D002839:Chromans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D013928:Thromboxane A2; D000077288:Troglitazone; D015232:Dinoprostone