Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production

doi:10.1084/jem.181.2.775

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Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production

TC van der Pouw Kraan, LC Boeije, RJ Smeenk, J Wijdenes and LA Aarden
Department of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.

During human immunodeficiency virus infection and allergic diseases, characterized by a dominant T helper (Th) 2 response, overproduction of prostaglandin E2 (PGE2) is observed. In this paper we studied the effect of PGE2 on interleukin (IL)-12 synthesis, because this cytokine has been described to be essential in induction of Th1 responses. IL-12 synthesis was induced in monocytes that were stimulated with Neisseria meningitidis-derived lipopolysaccharide in whole blood cultures. PGE2 almost completely inhibited lipopolysaccharide induced IL-12 production, whereas IL-6 production was only partially inhibited by PGE2. In contrast, the production of IL-10 was approximately twofold enhanced at these conditions. The effects of PGE2 were due to its cAMP- inducing capacity, since they could be mimicked by other cAMP inducers. Recombinant human IL-10 also inhibited IL-12 and IL-6 production. However, the inhibitory effect of PGE2 on IL-12 production was independent of IL-10 since neutralizing anti-IL-10 antibodies were unable to reverse this inhibition. These results suggest that the capacity of an antigen to induce PGE2 synthesis may play a crucial role in the development of either a Th1 or Th2 response.
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Gomi, K., Zhu, F.-G., Marshall, J. S. (2000). Prostaglandin E2 Selectively Enhances the IgE-Mediated Production of IL-6 and Granulocyte-Macrophage Colony-Stimulating Factor by Mast Cells Through an EP1/EP3-Dependent Mechanism. J. Immunol. 165: 6545-6552 [Abstract] [Full Text]
Chen, C.-H., Zhang, D.-H., LaPorte, J. M., Ray, A. (2000). Cyclic AMP Activates p38 Mitogen-Activated Protein Kinase in Th2 Cells: Phosphorylation of GATA-3 and Stimulation of Th2 Cytokine Gene Expression. J. Immunol. 165: 5597-5605 [Abstract] [Full Text]
Whittaker, D. S., Bahjat, K. S., Moldawer, L. L., Clare-Salzler, M. J. (2000). Autoregulation of Human Monocyte-Derived Dendritic Cell Maturation and IL-12 Production by Cyclooxygenase- 2-Mediated Prostanoid Production. J. Immunol. 165: 4298-4304 [Abstract] [Full Text]
Ramaswamy, K., Kumar, P., He, Y.-X. (2000). A Role for Parasite-Induced PGE2 in IL-10-Mediated Host Immunoregulation by Skin Stage Schistosomula of Schistosoma mansoni. J. Immunol. 165: 4567-4574 [Abstract] [Full Text]
HASKÓ, G., KUHEL, D. G., CHEN, J.-F., SCHWARZSCHILD, M. A., DEITCH, E. A., MABLEY, J. G., MARTON, A., SZABÓ, C. (2000). Adenosine inhibits IL-12 and TNF-{alpha} production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J. 14: 2065-2074 [Abstract] [Full Text]
SINIGAGLIA, F., D'AMBROSIO, D. (2000). Regulation of Helper T Cell Differentiation and Recruitment in Airway Inflammation. Am. J. Respir. Crit. Care Med. 162: S157-160 [Abstract] [Full Text]
Schmitt, D. A., Ullrich, S. E. (2000). Exposure to Ultraviolet Radiation Causes Dendritic Cells/Macrophages to Secrete Immune-Suppressive IL-12p40 Homodimers. J. Immunol. 165: 3162-3167 [Abstract] [Full Text]
KAPSENBERG, M. L., HILKENS, C. M. U., van der POUW KRAAN, T. C. M. T., WIERENGA, E. A., KALINSKI, P. (2000). Atopic Allergy: A Failure of Antigen-Presenting Cells to Properly Polarize Helper T Cells?. Am. J. Respir. Crit. Care Med. 162: S76-80 [Full Text]
STOKES PEEBLES, R. Jr., DWORSKI, R., COLLINS, R. D., JARZECKA, K., MITCHELL, D. B., GRAHAM, B. S., SHELLER, J. R. (2000). Cyclooxygenase Inhibition Increases Interleukin 5 and Interleukin 13 Production and Airway Hyperresponsiveness in Allergic Mice. Am. J. Respir. Crit. Care Med. 162: 676-681 [Abstract] [Full Text]
Hanna, N., Hanna, I., Hleb, M., Wagner, E., Dougherty, J., Balkundi, D., Padbury, J., Sharma, S. (2000). Gestational Age-Dependent Expression of IL-10 and Its Receptor in Human Placental Tissues and Isolated Cytotrophoblasts. J. Immunol. 164: 5721-5728 [Abstract] [Full Text]
Braun, M. C., Lahey, E., Kelsall, B. L. (2000). Selective Suppression of IL-12 Production by Chemoattractants. J. Immunol. 164: 3009-3017 [Abstract] [Full Text]
Kuroda, E., Sugiura, T., Zeki, K., Yoshida, Y., 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 [Abstract] [Full Text]
Ma, X., Sun, J., Papasavvas, E., Riemann, H., Robertson, S., Marshall, J., Bailer, R. T., Moore, A., Donnelly, R. P., Trinchieri, G., Montaner, L. J. (2000). Inhibition of IL-12 Production in Human Monocyte-Derived Macrophages by TNF. J. Immunol. 164: 1722-1729 [Abstract] [Full Text]
Demeure, C. E., Tanaka, H., Mateo, V., Rubio, M., Delespesse, G., Sarfati, M. (2000). CD47 Engagement Inhibits Cytokine Production and Maturation of Human Dendritic Cells. J. Immunol. 164: 2193-2199 [Abstract] [Full Text]