17β-estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte-derived macrophages
✍ Scribed by P. R. Kramer; S. F. Kramer; G. Guan
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 144 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
Abstract
Objective
Macrophages release cytokines, such as tumor necrosis factor α (TNFα), interleukin‐1 (IL‐1), and IL‐6, which modulate the symptoms of rheumatoid arthritis (RA). Macrophage release of these cytokines can be modulated by estrogen. Fcγ receptor type IIIA (CD16a) is a receptor expressed on macrophages that selectively binds IgG molecules, an important rheumatoid factor in RA. Binding of CD16 by anti‐CD16 monoclonal antibodies stimulates macrophage cytokine release. We undertook this study to test the hypothesis that decreased concentrations of estrogen (17β‐estradiol) directly cause an increase in CD16 expression, resulting in increased release of proinflammatory cytokines from monocytes and/or macrophages upon receptor binding.
Methods
THP‐1 cells and female human primary monocytes and monocyte‐derived macrophages were treated with no 17β‐estradiol, physiologic levels (1 × 10^−8^M) of 17β‐estradiol, or 1 × 10^−8^M 17β‐estradiol followed by withdrawal of 17β‐estradiol. Surface expression of CD16 and CD16 messenger RNA was measured using fluorescence‐activated cell sorting (FACS) and semiquantitative reverse transcription–polymerase chain reaction, respectively. Cytokine release from 17β‐estradiol–treated or untreated monocytes was then quantitated by enzyme‐linked immunosorbent assay and FACS after crosslinking the receptor with anti‐CD16 antibodies.
Results
CD16 transcript significantly increased in macrophage‐like THP‐1 cells and in primary, peripheral blood macrophages in the absence of 17β‐estradiol, and the observed increase in message was dependent on transcription. CD16 receptor levels on CD14+, transforming growth factor β–treated primary monocytes also increased in cells deprived of 17β‐estradiol. Analysis of the cytokines released showed that CD16 crosslinking stimulated significant increases in TNFα, IL‐1β, and IL‐6 due to the absence of estrogen.
Conclusion
Estrogen can modulate proinflammatory cytokine release from activated monocytes and/or macrophages, in part through modulation of CD16 expression.