17β-estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte-derived macrophages
17β-estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte-derived macrophages
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DOI：
10.1002/art.20309
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发表时间：
2004-06-01
影响因子：
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通讯作者：
Guan, G
中科院分区：
文献类型：
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作者：
Kramer, PR;Kramer, SF;Guan, G
Objective.巨噬细胞释放调节类风湿性关节炎（RA）症状的细胞因子，如肿瘤坏死因子α（TNF α）、白细胞介素-1（IL-1）和IL-6。巨噬细胞释放的这些细胞因子可以调节雌激素。Fc γ受体IIIA型（CD 16 a）是在巨噬细胞上表达的受体，其选择性地结合IgG分子，IgG分子是RA中的重要类风湿因子。抗CD 16单克隆抗体与CD 16的结合刺激巨噬细胞细胞因子的释放。我们进行了这项研究，以测试这一假设，即降低浓度的雌激素（17 β-雌二醇）直接导致CD 16表达的增加，从而增加释放促炎细胞因子从单核细胞和/或巨噬细胞受体结合。THP-1细胞和女性人原代单核细胞和单核细胞衍生的巨噬细胞用无17 β-雌二醇、生理水平（1 × 10（-8）M）的17 β-雌二醇或1 × 10（-8）M的17 β-雌二醇处理，随后停用17 β-雌二醇。CD 16和CD 16信使RNA的表面表达分别用荧光激活细胞分选（FACS）和半定量逆转录聚合酶链反应测定。用抗CD 16抗体交联受体后，通过酶联免疫吸附试验和流式细胞仪定量测定17 β-雌二醇处理或未处理的单核细胞释放的细胞因子。在缺乏17 β-雌二醇的情况下，巨噬细胞样THP-1细胞和原代外周血巨噬细胞中CD 16转录物显著增加，并且观察到的信息增加依赖于转录。在CD 14+、转化生长因子β处理的原代单核细胞上的CD 16受体水平在剥夺17 β-雌二醇的细胞中也增加。对释放的细胞因子的分析表明，由于缺乏雌激素，CD 16交联刺激TNF α、IL-1 β和IL-6的显著增加。雌激素可以调节促炎细胞因子从活化的单核细胞和/或巨噬细胞释放，部分通过调节CD 16表达。
Objective. Macrophages release cytokines, such as tumor necrosis factor alpha (TNFalpha), 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. Fcgamma 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 (17beta-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 17beta-estradiol, physiologic levels (1 X 10(-8)M) of 17beta-estradiol, or 1 X 10(-8)M 17beta-estradiol followed by withdrawal of 17beta-estradiol. Surface expression of CD16 and CD16 messenger RNA was measured using fluorescence-activated cell sorting (FACS) and semiquantitative reverse trans cription-polymerase chain reaction, respectively. Cytokine release from 17beta-estradiol-treated or untreated monocytes was then quantitated by enzyme-linked immunosorbent assay and FACS after crosslinking the receptor with antiCD16 antibodies.Results. CD16 transcript significantly increased in macrophage-like THP-1 cells and in primary, peripheral blood macrophages in the absence of 17beta-estradiol, and the observed increase in message was dependent on transcription. CD16 receptor levels on CD14+, transforming growth factor beta-treated primary monocytes also increased in cells deprived of 17beta-estradiol. Analysis of the cytokines released showed that CD16 crosslinking stimulated significant increases in TNFalpha, IL-1beta, 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.