Tim-4 Inhibits NO Generation by Murine Macrophages.

Tim-4 Inhibits NO Generation by Murine Macrophages.
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Tim-4 抑制小鼠巨噬细胞生成 NO

DOI:
10.1371/journal.pone.0124771
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Gao LF
Gao LF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xu LY;Qi JN;Liu X;Ma HX;Yuan W;Zhao PQ;Liang XH;Xu Y;Wang HX;Xu XY;Wang W;Ma CH;Gao LF

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T细胞免疫球蛋白和粘液域分子-4(TIM-4)作为免疫呼吸的潜在负调节剂,但是,其对巨噬细胞的调节尚未完全阐明这项研究旨在识别Tim-4在氮中的作用。 用100 ng/ml的LPS或100 ng/ml ifn-γ刺激了tim-4 mRNA表达。 TIM-4在干扰素 - γ(IFN-γ)模拟后的鼠巨噬细胞中上调。 - 诱导的核因子Kappa B(NF-κB) NF-κB抑制性配体在对比度上消除了巨噬细胞中的p65磷酸化。 这些结果表明,TIM-4参与巨噬细胞中无生产的负调节,这表明TIM-4在免疫疾病中的关键作用。
T cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) receives much attention as a potentially negative regulator of immune responses. However, its modulation on macrophages has not been fully elucidated so far. This study aimed to identify the role of Tim-4 in nitric oxide (NO) modulation. Macrophages were stimulated with 100 ng/ml LPS or 100 U/ml IFN-γ. RT-PCR was performed to detect TIM-4 mRNA expression. Tim-4 blocking antibody and NF-κB inhibitory ligand were involved in the study. NO levels were assayed by Griess reaction. Phosphorylation of NF-κB, Jak2 or Stat1 was verified by western blot. Tim-4 was up-regulated in murine macrophages after interferon-gamma (IFN-γ) stimulation. Tim-4 over-expression decreased NO production and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS) or IFN-γ-stimulated macrophages. Consistently, Tim-4 blockade promoted LPS or IFN-γ-induced NO secretion and iNOS expression. Tim-4 over-expression decreased LPS-induced nuclear factor kappa B (NF-κB) p65 phosphorylation in macrophages, which was abrogated by NF-κB inhibitory ligand. On the contrary, Tim-4 blocking increased LPS-induced NF-κB signaling, which was also abrogated by NF-κB inhibition. In addition, Tim-4 blockade promoted Jak2 and Stat1 phosphorylation in IFN-γ stimulated macrophages. These results indicate that Tim-4 is involved in negative regulation of NO production in macrophages, suggesting the critical role of Tim-4 in immune related diseases.
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