Vitamin A is a key regulator for cell growth, cytokine production, and differentiation in normal B cells.
In the present paper we demonstrate that retinol-retinol-binding protein and chylomicron remnant retinyl esters in concentrations normally found in human plasma inhibit growth of normal human B lymphocytes. Physiological concentrations of retinoic acid (about 30 nM) were less active than physiological concentrations of retinol (about 3 microM). Pharmacological concentrations of retinol and retinoic acid were more active than the concentrations normally found in plasma. Retinol (3 microM) inhibited anti-IgM-mediated DNA synthesis as measured by [3H]thymidine uptake at 72 h by 78%. Furthermore, we found that the cells were blocked in the mid-G1 phase of the cell cycle. Thus, neither MYC up-regulation measured at 3 h nor the expression of the early activation antigen 4F2 was reduced by retinol, whereas the late activation markers (transferrin receptor expression and actinomycin D staining at 48 h of stimulation) were markedly inhibited. Retinol reduced the interleukin 6 production induced by anti-IgM and interleukin 4 after 48 h, whereas the induction of interleukin 6 and tumor necrosis factor by O-tetradecanoylphorbol-13-acetate and ionomycin was less affected. We also noted that the retinoids reduced the formation of plaque-forming cells (i.e. Ig synthesis). These data imply that vitamin A present in human plasma is a normal modulator of B cell function.
Blomhoff
H K
HK
Department of Pathology, Norwegian Radium Hospital, Montebello, Oslo.
Smeland
E B
EB
Erikstein
B
B
Rasmussen
A M
AM
Skrede
B
B
Skjønsberg
C
C
Blomhoff
R
R
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002914:Chylomicrons / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D013936:Thymidine / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014801:Vitamin A / Q000494:pharmacology*
D002914:Chylomicrons; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D014801:Vitamin A; D014212:Tretinoin; D004247:DNA; D013936:Thymidine