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首页> 外文期刊>Biochemical Pharmacology >Janus kinase inhibitor ruxolitinib blocks thymic regeneration after acute thymus injury
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Janus kinase inhibitor ruxolitinib blocks thymic regeneration after acute thymus injury

机译：Janus激酶抑制剂Raxolitinib阻断急性胸腺损伤后的胸腺再生

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摘要

Thymic epithelial cells (TECs) are crucial for the production of T-cells. Cancer therapies including cytotoxic drugs and ionizing radiations damage TECs resulting in abnormal T-cell production and function. Fortunately, TECs can regenerate after injury. The Janus kinase (Jak) pathway is important in supporting survival of TECs. Jak inhibitors are used to treat cancer and immune disorders. The impact of Jak inhibitors on recovery of TECs is unknown. We induced acute thymus injury in mice by using ionizing radiation and evaluated the impact of ruxolitinib on thymus regeneration. We also tested if ruxolitinib affected proliferation of TECs in vitro. An increase was observed in the recovery of thymus cells after acute injury in association with up-regulation of TEC-related growth factors including keratinocyte growth factor (Kgf), epidermal growth factor (Egf), insulin-like growth factor 1 (Igf1) and receptor activator of NF-kappa B ligand (Rankl). Giving ruxolitinib decreased levels of receptors of these growth factors on TECs and blocked growth factor-induced recovery of thymus cells in damaged thymii. Ruxolitinib also blocked growth factors-induced proliferation of TECs in vitro. Thymus regeneration was inhibited when ruxolitinib was given immediately after thymus injury but not when it was given 1 week later. These data may have implications for how ruxolitinib is used in clinical practices.
机译：胸腺上皮细胞（TECS）对于生产T细胞至关重要。癌症疗法，包括细胞毒性药物和电离辐射损伤TECS，导致T细胞产生异常。幸运的是，TECS受伤后可以再生。 Janus激酶（Jak）途径对于支持TECS的存活是重要的。 JAK抑制剂用于治疗癌症和免疫障碍。 JAK抑制剂对TECS恢复的影响是未知的。我们通过使用电离辐射诱导小鼠急性胸腺损伤，并评估罗克兰替尼对胸腺再生的影响。我们还测试了ruxolitinib是否影响了体外TECS的增殖。在与包括角质形成细胞生长因子（KGF），表皮生长因子（EGF），胰岛素样生长因子1（IGF1）和胰岛素样生长因子1（IGF1）和胰岛素样生长因子1（IGF1）和胰岛素样生长因子（IGF1）和NF-Kappa B配体（RANKL）的受体激活剂。将Ruxolitinib降低了这些生长因子的受体水平，并阻断了胸腺嘧啶中的胸腺细胞的抑制因子诱导的胸腺细胞恢复。 Ruxolitinib还阻止了体外增殖的生长因子诱导的TECS增殖。当胸腺损伤后立即给出ruxolitinib但在1周后给出时，抑制胸腺再生抑制胸腺再生。这些数据可能对ruxolitinib如何在临床实践中使用的影响。

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