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Estrogen receptor functions in monocytic cytokine release induced by rheumatoid factor receptor activation (CD16)
Author(s) -
Kramer Phillip,
Hoot Vanessa,
Kramer Shan
Publication year - 2006
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.20.5.a967
Subject(s) - cd16 , estrogen receptor , estrogen , endocrinology , medicine , receptor , cytokine , chemistry , biology , immunology , antigen , cd3 , cancer , breast cancer , cd8
IgG molecules are an important rheumatoid factor in the autoimmune disease rheumatoid arthritis. Fc gamma RIII‐A (CD16) is a receptor expressed on monocytes and macrophages that selectively binds and is activated by IgG molecules. Release of cytokines from monocytes and macrophages due to CD16 receptor activation is modulated by estrogen thus, estrogen can impact autoimmune disease symptoms by modulating this receptor. The objective of this study was to test the hypothesis that estrogen directly causes a change in CD16 expression in monocytes and/or macrophages due to estrogen receptor binding. Monocytes were treated with physiological levels (1X10 −8 M and 1X10 −9 M) of 17‐ β‐estradiol and the estrogen receptor antagonist ICI 172,280. Activation of and cytokine release from primary, human, female monocytes was completed by crosslinking the CD16 receptor using an anti‐CD16 antibody. Consistent with previous results 17‐ β‐estradiol significantly reduced TNF‐α and IL‐1 β production and release upon crosslinking but ICI 172,280 blocked this effect. 17‐ β‐estradiol treatment significantly decreased CD16 transcript levels in monocytic cells and the observed decrease was attenuated by antagonist ICI 172,280 in a dose dependent manner. Chromatin immunoprecipitation (ChIP) assays detected estrogen receptor binding to the proximal promoter of the CD16. From these results we conclude estrogen can modulate cytokine release from monocytes and/or macrophages though modulation of CD16 expression and that action of estrogen requires, in part, the estrogen receptor. Our data are also consistent with the idea that the estrogen receptor acts at the CD16 promoter either by directly binding to the promoter or by indirectly binding to other transcription factors. This work was supported by NIH/NIDCR/ORWH.