Bailey Daniel P, Kashyap Mohit, Bouton L Andrew, Murray Peter J, Ryan John J
Department of Biology, Virginia Commonwealth University, Richmond, 23284-2012, USA.
J Leukoc Biol. 2006 Sep;80(3):581-9. doi: 10.1189/jlb.0405201. Epub 2006 Jul 7.
Interleukin (IL)-10 is a potent immunoregulatory cytokine capable of inhibiting the inflammatory response. As mast cells and macrophages are central effectors of inflammation, we investigated the effects of IL-10 on mast cell and macrophage development from mouse bone marrow progenitors. Bone marrow cells were cultured in IL-3 + stem cell factor (SCF), giving rise to mixed populations of mast cells and macrophages. The addition of IL-10 greatly decreased the expansion of bone marrow progenitor cells through a mechanism requiring signal tranducer and activator of transcription-3 expression. The inhibitory effects were a result of the induction of apoptosis, which occurred with caspase-3 activation and reduced mitochondrial membrane potential. Supporting a role for the mitochondrion, bone marrow cells from p53-deficient or Bcl-2 transgenic mice were partly resistant to the effects of IL-10. Further, IL-10 decreased Kit receptor expression and inhibited survival signaling by SCF or IL-3. These data indicate that IL-10 induces an intrinsic, mitochondrial apoptosis cascade in developing mast cells and macrophages through mechanisms involving blockade of growth factor receptor function. The ability of IL-10 to inhibit survival could support immune homeostasis by dampening inflammatory responses and preventing chronic inflammation.
白细胞介素（IL）-10是一种能够抑制炎症反应的强效免疫调节细胞因子。由于肥大细胞和巨噬细胞是炎症的主要效应细胞，我们研究了IL-10对小鼠骨髓祖细胞向肥大细胞和巨噬细胞发育的影响。将骨髓细胞培养于IL-3加干细胞因子（SCF）中，可产生肥大细胞和巨噬细胞的混合群体。添加IL-10通过一种需要信号转导和转录激活因子3表达的机制，极大地减少了骨髓祖细胞的扩增。这种抑制作用是细胞凋亡诱导的结果，细胞凋亡伴随着半胱天冬酶-3激活和线粒体膜电位降低。p53缺陷或Bcl-2转基因小鼠的骨髓细胞对IL-10的作用有部分抗性，这支持了线粒体的作用。此外，IL-10降低了Kit受体表达，并抑制了SCF或IL-3介导的存活信号。这些数据表明，IL-10通过涉及阻断生长因子受体功能的机制，在发育中的肥大细胞和巨噬细胞中诱导一种内在的线粒体凋亡级联反应。IL-10抑制存活的能力可通过减轻炎症反应和预防慢性炎症来支持免疫稳态。
