Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma.
Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma.
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DOI：
10.4049/jimmunol.145.3.940
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发表时间：
1990-08
影响因子：
4.4
通讯作者：
A. Ding;C. Nathan;J. Graycar;R. Derynck;D. Stuehr;S. Srimal
中科院分区：
文献类型：
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作者：
A. Ding;C. Nathan;J. Graycar;R. Derynck;D. Stuehr;S. Srimal
巨噬细胞失活因子 (MDF) 和转化生长因子-β 家族的三个成员（TGF-β 1、-β 2 和 -β 3）阻断 IFN-γ 诱导小鼠腹膜巨噬细胞释放活性氮中间体的能力。提高 IFN-γ 浓度并不会降低抑制剂的效力（约 7 nM MDF、2 pM TGF-β 1、4 pM TGF-β 2 和 8 pM TGF-β 3 抑制 50%）。这些抑制剂部分阻断了IFN-γ+TNF-α组合激活的巨噬细胞中亚硝酸盐释放的诱导，但当IFN-γ+LPS组合激活巨噬细胞时不能抑制。 MDF 和 TGF-β 1、-β 2 和 -β 3 仅在诱导阶段存在时才能抑制 IFN-γ 诱导的亚硝酸盐释放；一旦IFN-γ-亚硝酸盐开始释放，添加相同的细胞因子就不再具有抑制作用。在 48 小时内最大程度地抑制合成需要抑制剂在诱导的前 3 小时内存在。因此，细胞因子可以抑制并诱导巨噬细胞合成活性氮中间体、具有细胞毒性、抗菌和血管舒张特性的产物。
Macrophage deactivating factor (MDF) and three members of the transforming growth factor-beta family (TGF-beta 1, -beta 2, and -beta 3) blocked the ability of IFN-gamma to induce release of reactive nitrogen intermediates from mouse peritoneal macrophages. Raising the concentration of IFN-gamma did not diminish the potency of the inhibitors (50% inhibition by approximately 7 nM MDF, 2 pM TGF-beta 1, 4 pM TGF-beta 2, and 8 pM TGF-beta 3). These inhibitors partially blocked induction of nitrite release in macrophages activated with the combination of IFN-gamma plus TNF-alpha, but were incapable of inhibiting when macrophages were activated by the combination of IFN-gamma plus LPS. MDF and TGF-beta 1, -beta 2, and -beta 3 inhibited IFN-gamma-induced nitrite release only if present during the induction phase; once IFN-gamma-nitrite release had commenced, addition of the same cytokines was no longer inhibitory. Maximum inhibition of synthesis over a 48-h period required that the inhibitors be present during the first 3 h of induction. Thus, cytokines can suppress as well as induce macrophage synthesis of reactive nitrogen intermediates, products with cytotoxic, antimicrobial, and vasodilatory properties.