17β-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. (C) 2004 by The American Society of Hematology.