人中性粒细胞中糖皮质激素受体β含量高，使它们能够降低对糖皮质激素反应的细胞自发死亡率。
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Strickland I, Kisich K, Hauk PJ, Vottero A, Chrousos GP, Klemm DJ, Leung DY
人中性粒细胞中糖皮质激素受体β含量高，使它们能够降低对糖皮质激素反应的细胞自发死亡率。
中华医学杂志2001年3月5日;193(5):585-93。
- PubMed ID
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11238589 (在PubMed］
- 摘要
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中性粒细胞对糖皮质激素的敏感性明显低于T细胞，这使得在中性粒细胞介导的疾病中很难控制炎症。对不同激素反应机制的理解将有助于开发针对此类疾病的新的抗炎策略。人类糖皮质激素受体(GR)存在两种蛋白质亚型，GRalpha和GRbeta，它们来自于GR pre-mRNA初级转录本的选择性剪接。GRbeta不与糖皮质激素结合，是GRalpha活性的抑制剂。因此，这两种GRs的相对数量可以决定糖皮质激素的敏感性水平。在这项研究中，研究了人中性粒细胞和外周血单个核细胞(PBMCs)，以确定每种GR亚型的相对数量。免疫荧光分析GRalpha的平均荧光强度(MFI)分别为475 +/- 62和985 +/- 107。对于GRbeta, PBMCs和中性粒细胞的MFI分别为350 +/- 60和1389 +/- 143 (P < 0.05)。白细胞介素(IL)-8刺激中性粒细胞后，GRbeta染色强度增加至2,497 +/- 140 (P < 0.05)。无观察到GRalpha表达变化。 This inversion of the GRalpha/GRbeta ratio in human neutrophils compared with PBMCs was confirmed by quantitative Western analysis. Increased GRbeta mRNA expression in neutrophils at baseline, and after IL-8 exposure, was observed using RNA dot blot analysis. Increased levels of GRalpha/GRbeta heterodimers were found in neutrophils as compared with PBMCs using coimmunoprecipitation/Western analysis. Transfection of mouse neutrophils, which do not contain GRbeta, resulted in a significant reduction in the rate of cell death when treated with dexamethasone.We conclude that high constitutive expression of GRbeta by human neutrophils may provide a mechanism by which these cells escape glucocorticoid-induced cell death. Moreover, upregulation of this GR by proinflammatory cytokines such as IL-8 further enhances their survival in the presence of glucocorticoids during inflammation.