title: Estrogen selectively regulates chemokines in murine splenocytes.
abstract: Estrogen has striking effects on immunity and inflammatory autoimmune conditions. One potential mechanism of estrogen-induced regulation of immunity and inflammatory autoimmune conditions is by altering the secretion of chemokines by lymphocytes, an aspect not well addressed thus far. We found that estrogen has marked, but differential, effects on the secretion of chemokines from activated splenocytes. Estrogen treatment significantly increased the secretion of MCP-1, MCP-5, eotaxin, and stromal cell-derived factor 1beta from Con A-activated splenocytes when compared with placebo-treated controls, and it had no effects on the levels of RANTES, thymus and activation-regulated chemokine, and keratinocyte-derived chemokine (KC) at 24 h. A kinetic analysis showed that chemokines tended to increase with stimulation time, but only MCP-1 and MCP-5 showed a biological trend of increasing in splenocytes from estrogen-treated mice, and KC was decreased significantly in estrogen-treated splenocytes at 18 h. Estrogen did not affect the protein levels of chemokine receptors CCR1 or CCR2 at 24 h. Estrogen-induced alterations in the levels of MCP-1 and MCP-5 are mediated, in part, by IFN-gamma, as estrogen treatment of IFN-gamma null mice, unlike wild-type mice, did not up-regulate these chemokines. However, addition of recombinant IFN-gamma resulted in markedly increased secretion of MCP-1 and MCP-5 only in the cells derived from estrogen-treated mice. These studies provide novel data indicating that estrogen may promote inflammatory conditions by altering the levels of chemokines, providing evidence for an additional mechanism by which estrogens can regulate inflammation.
authors.affiliation: Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, 1410 Prices Fork Road, Blacksburg, VA 24061-0342, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Lengi
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Phillips
authors.forename: Ebru
authors.initials: E
authors.lastname: Karpuzoglu
authors.forename: S Ansar
authors.initials: SA
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D054377:Chemokine CXCL12; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D008297:Male; D051379:Mice; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism*
chemical_list: D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D004967:Estrogens; D019707:Receptors, Chemokine; D007371:Interferon-gamma