Assay System for the Effect of Prostaglandin E2 in the Determination of Polarized Cytokine Production

  • Etsushi Kuroda
  • Uki Yamashita
Part of the Methods in Molecular Biology book series (MIMB, volume 249)


The activation of CD4+ T-cell subsets, Th1 and Th2, is one of the most important focuses of immunology. Th1 and Th2 are differentiated from naive T cells after antigenic stimulation by the influence of cytokines [interleukin 12 (IL-12)/interferon-γ (IFN-γ) in Th1 and IL-4/IL-13 in Th2] or costimulatory molecules (CD80/CD86) provided from antigen presenting cells (APC), and have several important immunological functions (1). Recently, several reports have shown that chemical mediators, such as prostaglandins (PG) and histamine, also affect Th1/Th2 cytokine production and Th differentiation (2, 3, 4, 5, 6, 7). PGE2 is one of prostanoids produced by action of the enzyme cyclooxygenase (COX) on arachidonic acid. PGE2 is mainly produced by APC: monocytes, macrophages, and dendritic cells in the immune system (2). PGE2 has a suppressive effect on Th1-related cytokine productions such as IL-12 and IFN-γ by T cells, NK cells, and APCs, and an enhancing effect on Th2 development and activation.


Spleen Cell Chemokine Production Mouse Spleen Cell Disodium Hydrogen Phosphate Alkaline Phosphatase Substrate 
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  1. 1.
    O’Garra, A. (1998) Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8, 275–283.CrossRefGoogle Scholar
  2. 2.
    Phipps, R. P., Stein, S. H., and Roper, R. L. (1991) A new view of prostaglandin E regulation of the immune response. Immunol. Today 12, 349–352.PubMedCrossRefGoogle Scholar
  3. 3.
    Snijdewint, F. G. M., Kalinski, P., Wierenga, E. A., Bos, J. D., and Kapsenberg, M. L. (1993) Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J. Immunol. 150, 5321–5329.PubMedGoogle Scholar
  4. 4.
    Katamura, K., Shintaku, N., Yamauchi, Y., et al. (1995) Prostaglandin E2 at priming of naive CD4+ T cells inhibits acquisition of ability to produce IFN-γ and IL-2, but not IL-4 and IL-5. J. Immunol. 155, 4604–4612.PubMedGoogle Scholar
  5. 5.
    Tineke, C. T. M., Kraan, V. D. P., Boeije, L. C. M., Smeenk, R. J. T., Wijdenes, J., and Aarden, L. A. (1995) Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production. J. Exp. Med. 181, 775–779.CrossRefGoogle Scholar
  6. 6.
    Hilkens, C. M., Snijders, A., Vermeulen, H., et al. (1996) Accessory cell-derived IL-12 and prostaglandin E2 determine the IFN-γ level of activated human CD4+ T cells. J. Immunol. 156, 1722–1727.PubMedGoogle Scholar
  7. 7.
    Kuroda, E., Sugiura, T., Zeki, K., Yoshida, Y., and Yamashita, U. (2000) Sensitivity difference to the suppressive effect of prostaglandin E2 among mouse strains: a possible mechanism to polarize Th2 type response in BALB/c mice. J. Immunol. 164, 2386–2395.PubMedGoogle Scholar
  8. 8.
    Zlotnik, A. and Yoshie, O. (2000) Chemokines: a new classification system and their role in immunity. Immunity 12, 121–127.PubMedCrossRefGoogle Scholar
  9. 9.
    Bonecchi, R., Bianchi, G., Bordignon, P. P., et al. (1998) Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J. Exp. Med. 187, 129–134.PubMedCrossRefGoogle Scholar
  10. 10.
    Kuroda, E., Sugiura, T., Okada, K., Zeki, K., and Yamashita, U. (2001) Prostaglandin E2 up-regulates macrophage-derived chemokine production but suppresses IFN-inducible protein-10 production by APC. J. Immunol. 166, 1650–1658.PubMedGoogle Scholar
  11. 11.
    De Freitas, L. A. R., Mbow, M. L., Estay, M., Bleyenberg, J. A., and Titus, R. G. (1999) Indomethacin treatment slow disease progression and enhances a Th1 response in susceptible BALB/c mice infected with Leishmania major. Parasite Immunol. 21, 273–277.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2004

Authors and Affiliations

  • Etsushi Kuroda
    • 1
  • Uki Yamashita
    • 1
  1. 1.Department of Immunology, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan

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