骨形态发生蛋白-6 诱导巨噬细胞中诱导型一氧化氮合酶的表达。
Bone morphogenetic protein-6 induces the expression of inducible nitric oxide synthase in macrophages.
机构信息
Urologic Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.
出版信息
Immunology. 2009 Sep;128(1 Suppl):e758-65. doi: 10.1111/j.1365-2567.2009.03079.x. Epub 2009 Feb 17.
Abstract
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily. In the present study, we investigated the effect of BMPs on the production of inducible nitric oxide synthase (iNOS) in the murine macrophage cell line, RAW 264.7, and in mouse peritoneal macrophages. Among the BMPs, only BMP-6 induced iNOS expression in a time-dependent and dose-dependent manner in both cell types. Induction of iNOS was inhibited by both cycloheximide and actinomycin D, indicating that the induction of iNOS expression by BMP-6 requires new protein synthesis. Mechanistic studies revealed that the BMP-6-induced iNOS expression requires both Smads and nuclear factor-kappa B (NF-kappaB) signalling pathways. Furthermore, induction of interleukin-1beta (IL-1beta) was necessary for iNOS induction by BMP-6. These observations suggest that BMP-6 stimulates macrophages to produce iNOS through IL-1beta via Smad and NF-kappaB signalling pathways and that BMP-6 may be an important regulator of macrophages.
摘要
骨形态发生蛋白（BMPs）是转化生长因子-β（TGF-β）超家族的成员。在本研究中，我们研究了 BMPs 对鼠巨噬细胞系 RAW 264.7 和小鼠腹腔巨噬细胞中诱导型一氧化氮合酶（iNOS）产生的影响。在 BMPs 中，只有 BMP-6 以时间和剂量依赖的方式诱导两种细胞类型中的 iNOS 表达。iNOS 的诱导被环己酰亚胺和放线菌素 D 抑制，表明 BMP-6 诱导 iNOS 表达需要新的蛋白质合成。机制研究表明，BMP-6 诱导的 iNOS 表达需要 Smads 和核因子-κB（NF-κB）信号通路。此外，BMP-6 诱导白细胞介素-1β（IL-1β）对于 BMP-6 诱导 iNOS 是必需的。这些观察结果表明，BMP-6 通过 Smad 和 NF-κB 信号通路通过 IL-1β 刺激巨噬细胞产生 iNOS，并且 BMP-6 可能是巨噬细胞的重要调节剂。
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