Novel Eicosanoid Activators of PPARγ Formed by Raw 264.7 Macrophage Cultures

  • Sven Hammarstrom
  • Cecilia Trinks
  • Jane Wigren
  • Sailesh Surapureddi
  • Matts Soderstrom
  • Christopher K. Glass
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)

Abstract

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.

Keywords

HPLC Glycerol Glutathione Prostaglandin Hydrochloride 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fitzpatrick, F.A., and Wynalda, M.A. (1983) J. Biol. Chem. 258, 11713–8PubMedGoogle Scholar
  2. 2.
    Kikawa, Y., Narumiya, S., Fukushima, M., Wakatsuka, H., and Hayaishi, O. (1984) Proc. Natl. Acad. Sci. USA 81, 1317–21CrossRefGoogle Scholar
  3. 3.
    Kato, T., Fukushima, M., Kurozumi, S., and Noyori, R. (1986) Cancer Res 46, 3538–42PubMedGoogle Scholar
  4. 4.
    Narumiya, S., and Fukushima, M. (1986) J. Pharmacol. Exp. Ther. 239, 500–5PubMedGoogle Scholar
  5. 5.
    Narumiya, S., Ohno, K., Fujiwara, M. and Fukushima, M. (1986) J. Pharmacol. Exp. Ther. 239, 506–11PubMedGoogle Scholar
  6. 6.
    Narumiya, S., Ohno, K., Fukushima, M. and Fujiwara, M. (1987) J. Pharmacol. Exp. Ther. 242, 306–11Google Scholar
  7. 7.
    Forman, B. M., Tontonoz, P., Chen, J., Brun, R. P., Spiegelman, B. M., and Evans, R. M. (1995) Cell 83, 803–12PubMedCrossRefGoogle Scholar
  8. 8.
    Kliewer, S. A., Lenhard, J. M., Willson, T. M., Patel, I., Morris, D.C. and Lehmann, J. M. (1995) Cell 83, 813–9PubMedCrossRefGoogle Scholar
  9. 9.
    Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J., and Glass, C. K. (1998) Nature 391, 79–82PubMedCrossRefGoogle Scholar
  10. 10.
    Powell, W. S. (1982) Methods Enzymol. 86, 467–77PubMedCrossRefGoogle Scholar
  11. 11.
    Bundy, G. L., Morton, D. R., Peterson, D. C., Nishizawa, E. E., and Miller, W. L., (1983) J. Med. Chem. 26, 790–9PubMedCrossRefGoogle Scholar
  12. 12.
    DiRenzo, J., Söderström, M., Kurokawa, R., Ogliastro, M. H., Ricote, M., Ingrey, S., Hörlein, A., Rosenfeld, M. G., and Glass, C. K. (1997) Mol. Cell. Biol. 17, 2166–76PubMedCentralPubMedGoogle Scholar
  13. 13.
    Krey, G., Braissant, O., L Hornet, F., Kalkhoven, E., Perroud, M., Parker, M. G., and Wahli, W. (1997) Mol. Endrocrinology. 11, 779–91CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Sven Hammarstrom
    • 1
  • Cecilia Trinks
    • 1
  • Jane Wigren
    • 1
  • Sailesh Surapureddi
    • 1
  • Matts Soderstrom
    • 1
  • Christopher K. Glass
    • 2
  1. 1.Division of Cell BiologyLinkoping UniversityLinkopingSweden
  2. 2.Division of Cellular and Molecular MedicineUniversity of California at San DiegoLa JollaCA

Personalised recommendations