J. Biol. Chem., Vol. 267, Issue 33, 23988-23992, 11, 1992
Vitamin A is a key regulator for cell growth, cytokine production, and differentiation in normal B cells
HK Blomhoff, EB Smeland, B Erikstein, AM Rasmussen, B Skrede, C Skjonsberg and R Blomhoff
Department of Pathology, Norwegian Radium Hospital, Montebello, Oslo.
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.
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