Retinoic acid inhibits CD40 plus IL-4 mediated IgE production through alterations of sCD23, sCD54 and IL-6 production

Abstract

All-trans retinoic acid (ATRA) inhibits IgE synthesis from anti-CD40 plus IL-4 stimulated human B lymphocytes. To study the underlying mechanisms, we examined here molecules which are known to have an impact on IgE production, namely CD23, CD54 and IL-6. Human anti-CD40 plus IL-4 stimulated B cells were cultured in the absence and presence of ATRA (10(-6)-10(-10) M). ELISAs were performed to determine soluble (s) CD23 and sCD54, IL-6 and IgE-levels. CD23 and CD54 surface expression were determined by flow cytometric analysis. Semiquantitative-RT-PCR was employed to analyse IL-6, CD23 and CD54 mRNA expression. ATRA induced a dose-dependent increase of percent CD23 (3.4 fold) or CD54 (1.6 fold) positive B cells. At the mRNA level, this was reflected by a modest increase of CD54 mRNA (46.5 +/- 15.8%) only. By contrast, levels of sCD54 were decreased dose-dependently in the presence of ATRA (56.6 +/- 7.6%). Cytokine analysis showed that IL-6 secretion was significantly inhibited by ATRA (53.6 +/- 0.6%) and also IL-6 mRNA synthesis was reduced (66.3 +/- 11.6%). The observed inhibition of IgE production mediated by ATRA was significantly reversed to 90.5 +/- 12% by the addition of 100 pg/mL recombinant IL-6. ATRA interferes through several pathways with the anti-CD40 plus IL-4 mediated B cell activation, namely IL-6, CD23 and CD54.