Retinoic acid inhibits CD40 plus IL-4 mediated IgE production through alterations of sCD23, sCD54 and IL-6 production.
BACKGROUND
All-trans retinoic acid (ATRA) inhibits IgE synthesis from anti-CD40 plus IL-4 stimulated human B lymphocytes.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
ATRA interferes through several pathways with the anti-CD40 plus IL-4 mediated B cell activation, namely IL-6, CD23 and CD54.
Scheffel
F
F
Department of Dermatology and Allergy, Charité-Medical School Berlin, Schumannstrasse 20-21, 10117 Berlin, Germany.
Heine
G
G
Henz
B M
BM
Worm
M
M
D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology*
D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D015850:Interleukin-6; D012333:RNA, Messenger; D017455:Receptors, IgE; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D007073:Immunoglobulin E; D014212:Tretinoin