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

• Published in: Inflammation research 2005-03, Vol.54 (3), p.113-118
• Main Authors: Scheffel, F, Heine, G, Henz, B M, Worm, M
• Format: Article
• Language: English
• Subjects: Antigens, Differentiation, B-Lymphocyte - metabolism; B-Lymphocytes - metabolism; CD40 Antigens - biosynthesis; CD40 Antigens - metabolism; Cells, Cultured; Cytokines - metabolism; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Immunoglobulin E - chemistry; Immunoglobulin E - metabolism; Immunoglobulins - metabolism; Intercellular Adhesion Molecule-1 - metabolism; Interleukin-4 - metabolism; Interleukin-6 - metabolism; Leukocytes, Mononuclear - cytology; Protein Binding; Receptors, IgE - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Signal Transduction; Tretinoin - chemistry; Tretinoin - pharmacology
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-004-1331-8

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.