17beta-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells

The effects of estrogen on the immune system are still largely unknown. We have investigated the effect of 17beta-estradiol (E(2)) on human monocyte-derived immature dendritic cells (iDCs). Short-term culture in E(2) had no effect on iDC survival or the expression of cell surface markers. However, E(2) treatment significantly increased the secretion of interleukin 6 (IL-6) in iDCs and also increased secretion of osteoprotegerin (OPG) by DCs. Furthermore, E(2) significantly increased secretion of the inflammatory chemokines IL-8 and monocyte chemoattractant protein 1 (MCP-1) by iDCs, but not the production of the constitutive chemokines thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). However, after E(2) pretreatment the lipopolysaccharide (LPS)-induced production of MCP-1, TARC, and MDC by DCs was clearly enhanced. Moreover, mature DCs pretreated with E(2) stimulated T cells better than control cells. Finally, we found that E(2) provides an essential signal for migration of mature DCs toward CCL19/macrophage inflammatory protein 3beta (MIP3beta). In summary, E(2) may affect DC regulation of T-cell and B-cell responses, as well as help to sustain inflammatory responses. This may explain, in part, the reason serum levels of estrogen correlate with the severity of certain autoimmune diseases.