Estrogen selectively regulates chemokines in murine splenocytes

• Published in: Journal of leukocyte biology Vol. 81; no. 4; pp. 1065 - 1074
• Main Authors: Lengi, Andrea J., Phillips, Rebecca A., Karpuzoglu, Ebru, Ahmed, S. Ansar
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.04.2007
• Subjects: Animals; Cells, Cultured; Chemokine CCL5 - metabolism; Chemokine CXCL12; Chemokines - metabolism; Chemokines - secretion; Chemokines, CC - metabolism; Cytokines - metabolism; eotaxin; Estrogens - pharmacology; Gene Expression Regulation; inflammation; Interferon-gamma - genetics; Interferon-gamma - pharmacology; Interferon-gamma - physiology; Male; MCP‐1; MCP‐5; Mice; RANTES; Receptors, Chemokine - metabolism; SDF‐1β; Spleen - cytology; Spleen - metabolism
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0606391

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 1β 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‐γ, as estrogen treatment of IFN‐γ null mice, unlike wild‐type mice, did not up‐regulate these chemokines. However, addition of recombinant IFN‐γ 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.