Interleukin-12 inhibits eosinophil differentiation from bone marrow stem cells in an interferon-gamma-dependent manner in a mouse model of asthma.
Interleukin-12 inhibits eosinophil differentiation from bone marrow stem cells in an interferon-gamma-dependent manner in a mouse model of asthma.
复制标题
在哮喘小鼠模型中，Interleukin-12 以干扰素-γ 依赖性方式抑制骨髓干细胞的嗜酸性粒细胞分化。
DOI：
10.1046/j.0954-7894.2002.01350.x
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Sur,S
中科院分区：
文献类型：
--
作者：
Rais,M;Wild,JS;Choudhury,BK;Alam,R;Stafford,S;Dharajiya,N;Sur,S
背景在哮喘小鼠肺模型中，肺内给予IL-12已被证明可以抑制嗜酸性粒细胞的数量，但这种抑制的确切机制尚未报道。本研究的目的是探讨IL-12治疗是否抑制骨髓嗜酸性粒细胞生成，并阐明IFN-γ在此过程中的作用。目的阐明IL-12在体内外对小鼠骨髓（BM）干细胞向嗜酸性粒细胞分化的影响，并探讨IFN-γ在此过程中的作用机制。方法过敏原致敏的BALB/c小鼠在过敏原激发时鼻内给予低剂量的IL-12，3天后测定BM中嗜酸性粒细胞的数量。体外测定了 IL-12 对 BM 细胞分化为嗜酸性粒细胞的直接作用。通过测量 BM 细胞培养物中 IL-12 对 IFN-γ 的诱导作用以及使用 IFN-γ KO 小鼠来评估 IFN-γ 的机制作用。 结果用肺内 IL-12（1 ng 或 10 ng）治疗过敏小鼠可使 BM 中的嗜酸性粒细胞减少 43%。使用 IL-3 + IL-5 体外培养过敏原致敏小鼠的 BM 细胞诱导嗜酸性粒细胞分化。在这些培养物中添加 IL-12 可抑制嗜酸性粒细胞分化，在 10 ng/mL IL-12 浓度时出现最大抑制 (45%)。 IL-12 诱导 BM 培养物产生 IFN-γ，但未能抑制 IFN-γ 敲除小鼠中的嗜酸性粒细胞分化，这表明 IFN-γ 具有关键的机制作用。结论本研究表明，IL-12 选择性抑制 BM 嗜酸性粒细胞生成，并且这种作用是由 IFN-γ 介导的。肺内 IL-12 对 BM 嗜酸性粒细胞生成具有抑制作用，这可能代表了 IL-12 在过敏性气道疾病中抗嗜酸性粒细胞作用的一种新机制。
BackgroundIntrapulmonary administration of IL‐12 has been shown to inhibit the number of eosinophils in lung murine models of asthma, but the precise mechanism of this inhibition has not been reported. The purpose of this study was to examine whether IL‐12 treatment inhibits bone marrow eosinophilopoiesis, and to elucidate the role of IFN‐γ in this process.ObjectiveTo elucidate thein vivoandin vitroeffects of IL‐12 on eosinophil differentiation from murine bone marrow (BM) stem cells, and to examine the mechanistic role of IFN‐γ in this process.MethodsAllergen‐sensitized BALB/c mice were administered low doses of intranasal IL‐12 at the time of allergen challenge, and the number of eosinophils in BM was determined 3 days later. The direct actions of IL‐12 on eosinophil differentiation from BM cells were determinedin vitro. The mechanistic role of IFN‐γ was assessed by measuring IFN‐γ induction by IL‐12 in BM cell cultures, and through the use of IFN‐γ KO mice.ResultsTreatment of allergic mice with intrapulmonary IL‐12 (1 ng or 10 ng) reduced eosinophils in BM by 43%. Culture of BM cells from allergen‐sensitized mice with IL‐3 + IL‐5 induced eosinophil differentiationin vitro. Addition of IL‐12 to these cultures inhibited eosinophil differentiation, with maximal inhibition (45%) occurring at 10 ng/mL IL‐12 concentration. IL‐12 induced IFN‐γ production from BM cultures, and failed to inhibit eosinophil differentiation in IFN‐γ‐knockout mice, indicating a critical mechanistic role for IFN‐γ.ConclusionThis study demonstrates that IL‐12 selectively inhibits BM eosinophilopoiesis, and that this effect is mediated by IFN‐γ. Intrapulmonary IL‐12 has suppressive effects on BM eosinophilopoiesis that may represent a novel mechanism contributing to the anti‐eosinophilic effects of IL‐12 in allergic airway disease.