JAK inhibitors AG-490 and WHI-P154 decrease IFN-gamma-induced iNOS expression and NO production in macrophages.
JAK inhibitors AG-490 and WHI-P154 decrease IFN-gamma-induced iNOS expression and NO production in macrophages.
复制标题
JAK抑制剂AG-490和WHI-P154降低了IFN-GAMMA诱导的iNOS表达，而在巨噬细胞中没有产生。
DOI：
10.1155/mi/2006/16161
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发表时间：
2006
影响因子：
4.6
通讯作者：
Moilanen, Eeva
中科院分区：
文献类型：
--
作者：
Sareila, Outi;Korhonen, Riku;Karpanniemi, Outi;Nieminen, Riina;Kankaanranta, Hannu;Moilanen, Eeva
在炎症中，诱导型一氧化氮合酶（iNOS）产生一氧化氮（NO），其调节炎症过程。我们研究了Janus激酶（JAK）抑制剂AG-490和WHI-P154对干扰素-γ（IFN-γ）刺激的J774小鼠巨噬细胞中iNOS表达和NO产生的影响。JAK抑制剂AG-490和WHI-P154降低IFN-γ诱导的细胞核信号转导和转录激活因子1α（STAT 1 α）水平。JAK抑制剂AG-490和WHI-P154也以浓度依赖性方式降低iNOS蛋白和mRNA表达以及NO产生。当通过放线菌素D测定时，JAK抑制剂均不影响iNOS mRNA的衰减。我们的结果表明，AG-490或WHI-P154抑制JAK-STAT 1通路导致IFN-γ刺激的巨噬细胞中iNOS表达和NO产生的减弱。
In inflammation, inducible nitric oxide synthase (iNOS) produces nitric oxide (NO), which modulates inflammatory processes. We investigated the effects of Janus kinase (JAK) inhibitors, AG-490 and WHI-P154, on iNOS expression and NO production in J774 murine macrophages stimulated with interferon-γ (IFN-γ). JAK inhibitors AG-490 and WHI-P154 decreased IFN-γ-induced nuclear levels of signal transducer and activator of transcription 1α (STAT1α). JAK inhibitors AG-490 and WHI-P154 decreased also iNOS protein and mRNA expression and NO production in a concentration-dependent manner. Neither of the JAK inhibitors affected the decay of iNOS mRNA when determined by actinomycin D assay. Our results suggest that the inhibition of JAK-STAT1-pathway by AG-490 or WHI-P154 leads to the attenuation of iNOS expression and NO production in IFN-γ-stimulated macrophages.