1alpha,25-dihydroxyvitamin D3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro.
In the present study, we examined whether anti-CD40+IL-4-mediated B cell proliferation and immunoglobulin synthesis is affected by vitamin D (VD) and its low-hypercalcemic analogue EB1089 in Bcells from healthy donors. Analysis of vitamin D receptor (VDR) expression showed that only anti-CD40+IL-4-stimulated, but not resting B cells express VDR. Studies on B cell proliferation revealed that anti-CD40+IL-4-mediated proliferation of B cells was not affected by VD or EB1089. By contrast, IgE synthesis was markedly inhibited by both, VD and EB1089, starting at concentrations from 10(-10) M for VD and 10(-12) M for EB1089, with maximal inhibition at 10(-6) M (VD 85.5+/-9.7%; EB1089 77.3+/-10.8%). The production of the other Ig (IgA and IgG) was not significantly inhibited by VD after anti-CD40+IL-4 stimulation, and IgM production was only slightly reduced (18.7+/-7.9%). These observations were confirmed by intracellular staining of the different isotypes in B cells after anti-CD40+IL-4 stimulation, which showed a strong reduction of IgE(+) cells in the presence of VD. Analyses of molecules that are known to affect IgE production (CD23 and IL-6) revealed that these are not involved in VD-dependent inhibition of IgE production. By contrast, epsilon germ-line transcription was inhibited by VD (41.2+/-26.1%; n=5), as was NF-kappaB (p50 and p65) protein expression in stimulated cells. These data show that VD and its analogue EB1089 inhibit IgE production of anti-CD40+IL-4-stimulated B cells in vitro. The involved mechanism includes epsilon germ-line transcription, NF-kappaB activation and switch recombination suggesting that complex mechanisms of VD action in anti-CD40+IL-4-stimulated B cells are responsible.
Heine
Guido
G
Department of Dermatology and Allergy, Charité, Humboldt University, Berlin, Germany.
Anton
Katrin
K
Henz
Beate M
BM
Worm
Margitta
M
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens / Q000276:immunology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004247:DNA / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D019013:CD40 Antigens; D007139:Immunoglobulin epsilon-Chains; D015850:Interleukin-6; D018167:Receptors, Calcitriol; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E; D004247:DNA; D002117:Calcitriol; C078903:seocalcitol