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Selective regulation of chemokine CXCL6 by estrogen receptorβ (ERβ)
Author(s) -
Scotland Ramona Sumintra,
Roy Bornali,
Duchene Johan,
Ahluwalia Amrita
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.718.3
Subject(s) - chemokine , cxcl1 , interleukin 8 , umbilical vein , ccl7 , agonist , ccl2 , chemokine receptor , ccl5 , estrogen receptor , endocrinology , biology , medicine , cancer research , chemistry , receptor , immunology , inflammation , in vitro , t cell , immune system , biochemistry , il 2 receptor , cancer , breast cancer
Endothelium‐derived chemokines are integral mediators of inflammatory cell recruitment and have been implicated in the pathogenesis of cardiovascular disease (CVD). Estrogens are thought to underlie the protective effects of female sex against CVD, although the exact mechanisms of this effect are uncertain. We investigated the hypothesis that estrogens inhibit endothelial chemokine production in response to an inflammatory stimulus. qPCR of human umbilical vein endothelial cells (HUVECs) confirmed presence of ERα (46kD variant), ERβ and GPR30 mRNA. IL‐1β (1ng/ml, 8h) treatment elevated CXCL1 (Groα, 370‐fold), CXCL5 (ENA78, 310‐fold), CXCL6 (GCP2, 1030‐fold), CXCL8 (IL8, 150‐fold), and CCL2 (MCP1, 30‐fold) expression in HUVECs. Whilst pre‐treatment of cells with the ERα agonist 4,4′,4″(4‐Propyl‐[1H]‐pyrazole‐1,3,5‐triyl)trisphenol (PPT, 1nM, 16h) had no effect on IL‐1β‐induced chemokine expression, treatment with the ERβ agonist 2,3‐bis(4‐hydroxyphenyl)‐propionitrile (DPN, 1nM, 16h) suppressed CXCL6 expression only (P<0.01, n=7). This effect was abolished by 1h pre‐treatment with ER antagonist ICI 182,780 (100nM, n=5). Thus our results show that activation of ERß but not ERα selectively inhibits endothelial CXCL6 expression; a response that likely contributes to the anti‐inflammatory actions of estrogens in vivo. Supported by Wellcome Trust.