title: 17beta-estradiol (E2) modulates cytokine and chemokine expression in human monocyte-derived dendritic cells.
abstract: 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.
authors.affiliation: Department of Microbiology, Box 357 242, University of Washington, Seattle, WA 98195, USA. asab@u.washington.edu
authors.forename: Asa K
authors.initials: AK
authors.lastname: Bengtsson
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ryan
authors.forename: Daniela
authors.initials: D
authors.lastname: Giordano
authors.forename: Dario M
authors.initials: DM
authors.lastname: Magaletti
authors.forename: Edward A
authors.initials: EA
authors.lastname: Clark
mesh_terms: D019013:CD40 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054414:Chemokine CCL17; D054415:Chemokine CCL19; D018932:Chemokine CCL2 / Q000378:metabolism; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000276:immunology* / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor
chemical_list: C106230:CCL17 protein, human; C515460:CCL19 protein, human; C515482:CCL22 protein, human; D019013:CD40 Antigens; D054414:Chemokine CCL17; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054422:Chemokine CCL22; D019742:Chemokines, CC; D016207:Cytokines; D006023:Glycoproteins; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D004958:Estradiol