Prostaglandin E2 promotes IL-4-induced IgE and IgG1 synthesis

R. L. Roper, D. H. Conrad, D. M. Brown, G. L. Warner, R. P. Phipps

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

PG of the E series are generally known to suppress immune responses, however, we have found that PGE synergizes with IL-4 to induce IgE and IgG1 production in LPS-stimulated murine B lymphocytes. PGE2 and PGE1 (10-6 to 10-8 M) significantly increase IgE and IgG1 production (up to 26-fold) at all concentrations of IL-4 tested. In addition to its effects on IgE and IgG1, PGE also causes a significant decrease in IgM and IgG3 synthesis, suggesting that PGE may promote IL-4-induced class switching. The specificity of the E series PG effect is demonstrated by the fact that PGF(2α) (10-6 M) does not alter production of any of these isotypes. Because PGE can mediate its effects through cAMP in some cases, we investigated the importance of cAMP levels in regulation of isotype expression. Other agents that increase intracellular cAMP levels (cholera toxin and dibutyryl cAMP) were assessed for their ability to regulate isotype differentiation. Cholera toxin (100 pg/ml) and dibutyryl cAMP (100 μM) significantly enhanced IgE and IgG1 production and diminished IgM and IgG3 synthesis. We also show that PGE and cholera toxin elevate intracellular cAMP in B lymphocytes in a dose-dependent manner. In contrast, PGF(2α) (10-6 M) and the B subunit of cholera toxin (100 pg/ml) did not increase cAMP and did not regulate the isotype of Ig produced, reiterating the importance of cAMP in enhancing isotype differentiation. Although PGE is known to inhibit a number of immune responses, our data show that it is not always inhibitory. PGE may play a role in atopy in vivo where PGE-secreting cells such as macrophages, follicular dendritic cells, and fibroblasts can promote IgE synthesis. This research emphasizes the importance of PGE in regulation of the humoral immune response and adds a new stimulatory action to the repertoire of known PGE effects.

Original languageEnglish (US)
Pages (from-to)2644-2651
Number of pages8
JournalJournal of Immunology
Volume145
Issue number8
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Roper, R. L., Conrad, D. H., Brown, D. M., Warner, G. L., & Phipps, R. P. (1990). Prostaglandin E2 promotes IL-4-induced IgE and IgG1 synthesis. Journal of Immunology, 145(8), 2644-2651.