The calcium-regulating hormone 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) is recognized as an immunomodulator. Members of the macrophage-monocyte lineage are targets for 1,25(OH)(2)D-3 action. The hormone enhances the ability of bone marrow-derived macrophages (BMDMs) to produce H2O2, increases the expression of the macrophage specific surface antigen MAC-2, increases the release of tumor necrosis factor-alpha (TNF-alpha), and inhibits BMDM proliferation. In the present study we examine the possibility that estrogen modulates 1,25(OH)(2)D-3 effects on BMDMs. The active form, 17 beta-estradiol, failed to affect any of the BMDM functions by itself. On the other hand, 17 beta-estradiol increased the effects of 1,25(OH)(2)D-3 production by BMDMs and on MAC-2 expression on these cells. The inactive estrogen analog 17 alpha-estradiol was unable to elicit these effects. Moreover, 17 beta-estradiol did not affect the lipopolysaccharide (LPS)-induced increase in H2O2 production by BMDMs. Modulation of BMDM proliferation and TNF-alpha release from these cells by 1,25(OH)(2)D-3 were not affected by the estrogen. The experiments were performed with BMDMs harvested from vitamin D-depleted and repleted mice, and always under similar conditions, the various functions were more pronounced in the cells derived from the repleted mice. Our data are consistent with the hypothesis that 17 beta-estradiol modulates the interactions of 1,25(OH)(2)D-3 with BMDMs and consequently is able to affect biological responses to 1,25(OH)(2)D-3 in these cells. We propose that this cell system is a convenient, nontransformed model for studying cellular activities of 1,25(OH)(2)D-3.
