Novel Eicosanoid Activators of PPARγ Formed by Raw 264.7 Macrophage Cultures
Prostaglandin D2 (PGD2) is a major arachidonic acid metabolite in mast cells, megakaryoblastic CMK cells and antigen presenting cells, for example various types of macrophages. It induces pulmonary vasoconstriction and bronchoconstriction. Increased formation of PGD2 may be responsible for the symptoms of mastocytosis, it may contribute to the development of allergic symptoms and there is evidence that PGD2 regulates sleep. In the presence of serum albumin, PGD2 is converted to several products (1,2) which exhibit antiproliferative properties. These prostaglandin J2 compounds have been proposed to bind to intracellular receptors and translocate to the cell nucleus (3-6). In 1995, one of the antiproliferative prostaglandins, 15-deoxy-Al2“4 —PGJ2 was suggested to be a natural ligand for peroxisome proliferator-activated receptor-y (PPAR y)and to play a role in the terminal differentiation of fat cells (7,8). Recent studies show that PGD2 inhibits the expression of the genes encoding inducible nitric oxide synthase, gelatinase B and LDL scavenger receptor RAW 264.7 macrophages (9). PGD2 itself is a poor PPARy ligand. Therefore, we assumed that the activity observed in (9) was mediated by PGD2 metabolites. The purpose of this investigation was to identify PGD2 metabolites which activate PPARy in macrophages.
KeywordsHPLC Glycerol Glutathione Prostaglandin Hydrochloride
Unable to display preview. Download preview PDF.
- 6.Narumiya, S., Ohno, K., Fukushima, M. and Fujiwara, M. (1987) J. Pharmacol. Exp. Ther. 242, 306–11Google Scholar