Functional interaction between beta 2-adrenoceptor agonists and interleukin-4 in the regulation of CD23 expression and release and IgE production in human
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N Paul-Eugene1, J P Kolb, A Calenda
1INSERM U196, Institut Curie, Paris, France.
Insights
Beta 2-adrenoceptor agonists enhance Interleukin-4 (IL-4)-induced IgE production in human cells. They achieve this by increasing soluble CD23 release and reducing Interferon-gamma (IFN-gamma) production.
Area of Science:
- Immunology
- Pharmacology
Background:
- Normal human peripheral blood mononuclear cells (PBMC) produce Immunoglobulin E (IgE) upon stimulation with Interleukin-4 (IL-4).
- Beta 2-adrenoceptor agonists are commonly used in respiratory medicine.
Purpose of the Study:
- To investigate the effect of beta 2-adrenoceptor agonists on IL-4-induced IgE production in human PBMC.
- To elucidate the mechanisms underlying the interaction between beta 2-adrenoceptor agonists and IL-4 signaling in immune cells.
Main Methods:
- Human PBMC and U937 cell line were cultured and stimulated with IL-4.
- Beta 2-adrenoceptor agonists (salbutamol, fenoterol) and antagonist (D,L-propranolol) were used to modulate cellular responses.
- Measurements included IgE production, soluble CD23 (sCD23) release, Interferon-gamma (IFN-gamma) production, and cell differentiation markers.
Main Results:
- Beta 2-adrenoceptor agonists potentiated IL-4-induced IgE production in human PBMC.
- These agonists enhanced the release of sCD23 and inhibited IFN-gamma production without affecting IL-4 levels.
- Beta 2-adrenoceptor agonists also enhanced IL-4-mediated CD23 expression and differentiation in U937 cells.
Conclusions:
- Beta 2-adrenoceptor agonists modulate IL-4-induced IgE production in humans via enhanced sCD23 release and suppressed IFN-gamma.
- The functional interaction between beta 2-adrenoceptor agonists and IL-4 is cell-type and differentiation-stage dependent.
- These findings suggest a role for beta 2-adrenoceptor agonists in influencing allergic responses.
Abstract:
Normal human peripheral blood mononuclear cells (PBMC) produced IgE when stimulated with IL-4. In the present report it was shown that beta 2-adrenoceptor agonists, salbutamol and fenoterol, potentiated the IL-4-induced IgE production without significantly affecting the expression of the low affinity receptor for IgE at the cell surface of monocytes and B lymphocytes. However, beta 2-adrenoceptor agonists were shown to enhance at day 7 the IL-4-induced release of the soluble form of CD23 (sCD23) by PBMC. This effect was specific since a beta-adrenoceptor antagonist, D,L-propranolol, inhibited the IL-4-induced IgE production by these cells. Alternatively, the beta 2-adrenoceptor agonists inhibited the production by these cells of interferon-gamma (IFN-gamma) but did not affect the production of IL-4 when stimulated with phytohemagglutinin A + a phorbol ester. These data suggest that beta 2-adrenoceptor agonists influence the IL-4-induced IgE production in humans by enhancing the release of sCD23 and inhibiting the production of endogenous IFN-gamma. In addition to the effect on the IL-4-induced IgE production it was shown that beta 2-adrenoceptor agonists potentiated the effect of IL-4 on a human promonocytic cell line, U 937, by enhancing CD23 expression and release and by inducing the differentiation of these cells into monocyte-like cells. Taken together, these data indicate that beta 2-adrenoceptor agonists potentiated the effect of IL-4 and that this functional interaction is different considering the cell-lineage and the stage of differentiation of these cells.