Modulation of vitamin D increased H₂O₂ production and MAC-2 expression in the bone marrow-derived macrophages by estrogen

The calcium-regulating hormone 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is recognized as an immunomodulator. Members of the macrophage-monocyte lineage are targets for 1,25(OH)₂D₃ 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-α (TNF-α), and inhibits BMDM proliferation. In the present study we examine the possibility that estrogen modulates 1,25(OH)₂D₃ effects on BMDMs. The active form, 17β-estradiol, failed to affect any of the BMDM functions by itself. On the other hand, 17β-estradiol increased the effects of 1,25(OH)₂D₃ production by BMDMs and on MAC-2 expression on these cells. The inactive estrogen analog 17α-estradiol was unable to elicit these effects. Moreover, 17β-estradiol did not affect the lipopolysaccharide (LPS)-induced increase in H₂O₂ production by BMDMs. Modulation of BMDM proliferation and TNF-α release from these cells by 1,25(OH)₂D₃ 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 17β-estradiol modulates the interactions of 1,25(OH)₂D₃ with BMDMs and consequently is able to affect biological responses to 1,25(OH)₂D₃ in these cells. We propose that this cell system is a convenient, nontransformed model for studying cellular activities of 1,25(OH)₂D₃.