Resveratrol ameliorates TNFα-mediated suppression of erythropoiesis in human CD34(+) cells via modulation of NF-κB signalling.
Resveratrol ameliorates TNFα-mediated suppression of erythropoiesis in human CD34(+) cells via modulation of NF-κB signalling.
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DOI：
10.1111/j.1365-2141.2011.08800.x
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发表时间：
2011-10
影响因子：
6.5
通讯作者：
Vanasse GJ
中科院分区：
文献类型：
--
作者：
Jeong JY;Silver M;Parnes A;Nikiforow S;Berliner N;Vanasse GJ
促炎细胞因子的过度表达，包括肿瘤坏死因子α（TNFα），与炎症性贫血的发病机制有关。 TNFα 通过对造血祖细胞的直接和间接影响来抑制红细胞集落形成，通常涉及核因子 (NF)-κB 信号的激活，导致对红细胞生成至关重要的转录因子的下调。对于许多炎症性贫血患者来说，缺乏有效且安全的治疗方法。白藜芦醇是在红酒葡萄中发现的一种黄烷醇，具有有效的抗炎特性，但对其对人类红细胞生成的影响的研究已证明是矛盾的。我们研究了白藜芦醇是否可以改善人类 CD34+ 造血祖细胞中 TNFα 介导的红细胞生成抑制。我们发现白藜芦醇部分逆转了 TNFα 的红细胞抑制作用，导致人 CD34+ 细胞中爆发形成单位红细胞集落形成显着恢复。在 TNFα 存在的情况下，将 CD34+ 细胞与白藜芦醇预孵育 72 小时，通过减少 NF-κB 核定位来抑制 NF-κB 活化，而不改变总 NF-κB 蛋白水平，且与 IκB 降解无关。白藜芦醇还显着恢复了经 TNFα 处理的 CD34+ 细胞中红系转录因子 NFE2 的基线表达和 GATA1/GATA2 比率。总之，白藜芦醇可能抑制 TNFα 介导的 NF-κB 激活并促进原代人 CD34+ 细胞的红细胞生成。
Overexpression of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFα), has been implicated in the pathogenesis of anaemia of inflammation. TNFα suppresses erythroid colony formation via both direct and indirect effects on haematopoietic progenitors, often involving activation of nuclear factor (NF)-κB signalling resulting in downregulation of transcription factors critical for erythropoiesis. There is a dearth of effective and safe therapies for many patients with inflammatory anaemia. Resveratrol is a flavanol found in red wine grapes that possesses potent anti-inflammatory properties, but studies of its impact on human erythropoiesis have proven contradictory. We investigated whether resveratrol ameliorates TNFα-mediated suppression of erythropoiesis in human CD34+ haematopoietic progenitors. We found that resveratrol partially reverses the erythroid suppressive effects of TNFα, leading to significant recovery in burst forming unit-erythroid colony formation in human CD34+ cells. CD34+ cells pre-incubated with resveratrol for 72 h in the presence of TNFα inhibited NF-κB activation via decreased NF-κB nuclear localization without altering total NF-κB protein levels and independent of IκB degradation. Resveratrol also significantly restored the baseline expression of erythroid transcription factors NFE2 and the GATA1/GATA2 ratio in CD34+ cells treated with TNFα. In conclusion, resveratrol may inhibit TNFα-mediated NF-κB activation and promote erythropoiesis in primary human CD34+ cells.