VITAMIN-A IS REQUIRED FOR REGULATION OF POLYMERIC IMMUNOGLOBULIN RECEPTOR (PLGR) EXPRESSION BY INTERLEUKIN-4 AND INTERFERON-GAMMA IN A HUMAN INTESTINAL EPITHELIAL-CELL LINE

The secretory immunoglobulin A (IgA) antibody response to infections o f mucosal surfaces requires transport of IgA from the basal to apical surface of mucosal epithelial cells by a specific transport protein, t he polymeric immunoglobulin receptor (plgR). We have tested the hypoth esis that the vitamin A metabolite all-trans retinoic acid (RA) is req uired for the regulation of plgR expression by the cytokines interleuk in-4 (IL-4) and interferon-gamma (IFN-gamma) in HT-29 cells, a well-di fferentiated human epithelial cell line derived from a colonic carcino ma. plgR expression is upregulated by lFN-gamma and IL-4 when HT-29 ce lls are grown in normal media, but this upregulation was significantly lower when cells were grown in vitamin A-depleted media. Treatment wi th RA at concentrations from 10(-9) to 10(-5) mol/L restored normal le vels of plgR expression. The percentages of cells expressing cell-surf ace plgR after 24, 48 and 72 h of treatment with RA, IL-4 and IFN-gamm a were 66 +/- 10, 90 +/- 5 and 92 +/- 1, respectively, significantly h igher than the percentages seen without RA treatment, which were 32 +/ - 2.3, 72 +/- 1.2 and 30 +/- 7, respectively. In addition, the intensi ty of fluorescence of plgR-positive cells was significantly higher in the RA-treated cultures than in the cultures without RA treatment. Sim ilarly, plgR mRNA levels (adjusted for beta-actin mRNA levels) in RA-s upplemented cultures were 404, 105 and 949% higher at 24, 48 and 72 h, respectively, than were plgR mRNA levels in identical cultures grown in the absence of RA. These data indicate that RA strongly interacts w ith IL-4 and IFN-gamma to regulate plgR expression in HT-29 cells, sug gesting that vitamin A may be required for proper in vivo regulation o f IgA transport in response to mucosal infections.