Bailey Daniel P, Kashyap Mohit, Mirmonsef Paria, Bouton L Andrew, Domen Jos, Zhu Jingfang, Dessypris Emmanuel N, Ryan John J
Department of Biology, Virginia Commonwealth University, Richmond, Va. 23284-2012, USA.
Exp Hematol. 2004 Jan;32(1):52-9. doi: 10.1016/j.exphem.2003.10.011.
The aim of this study was to assess the effects of interleukin-4 and signal transducer and activator of transcription (Stat)-6 on IL-3+SCF-induced mast cell development.
Unseparated mouse bone marrow cells were cultured in IL-3+SCF, giving rise to mast cells and monocytes/macrophages. The addition of IL-4, the use of Stat6-deficient bone marrow cells, and expression of a constitutively active Stat6 mutant were employed to assess the effects of IL-4 and Stat6 on cell viability, proliferation, and differentiation. Bax-deficient and bcl-2 transgenic bone marrow cells were used to assess the importance of the mitochondria in IL-4-mediated effects.
IL-4 elicited apoptosis and limited the cell cycle progression of developing bone marrow cells, without affecting cell differentiation. Apoptosis required that IL-4 be present during the first 8 days of the 21-day culture period. Cell death correlated with loss of mitochondrial membrane potential. Accordingly, IL-4-mediated apoptosis was inhibited by Bax deletion or bcl-2 overexpression. Lastly, Stat6 activation was both necessary and sufficient to inhibit cell survival.
IL-4 exerts potent apoptotic effects on developing mast cells and monocyte/macrophages through mitochondrial damage and Stat6 activation.
本研究旨在评估白细胞介素-4以及信号转导与转录激活因子（Stat）-6对白细胞介素-3+干细胞因子（SCF）诱导的肥大细胞发育的影响。
未分离的小鼠骨髓细胞在白细胞介素-3+SCF中培养，可产生肥大细胞以及单核细胞/巨噬细胞。通过添加白细胞介素-4、使用Stat6缺陷型骨髓细胞以及表达组成型活性Stat6突变体来评估白细胞介素-4和Stat6对细胞活力、增殖和分化的影响。使用Bax缺陷型和bcl-2转基因骨髓细胞来评估线粒体在白细胞介素-4介导的效应中的重要性。
白细胞介素-4引发凋亡并限制发育中的骨髓细胞的细胞周期进程，但不影响细胞分化。凋亡要求在21天培养期的前8天存在白细胞介素-4。细胞死亡与线粒体膜电位丧失相关。因此，Bax缺失或bcl-2过表达可抑制白细胞介素-4介导的凋亡。最后，Stat6激活对于抑制细胞存活既是必要的也是充分的。
白细胞介素-4通过线粒体损伤和Stat6激活对发育中的肥大细胞和单核细胞/巨噬细胞发挥强大的凋亡作用。
