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首页> 外文期刊>Cytokine >Role of type I interferons during macrophage activation by lipopolysaccharide.
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Role of type I interferons during macrophage activation by lipopolysaccharide.

机译:I型干扰素在脂多糖激活巨噬细胞过程中的作用。

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摘要

Activation of macrophages by bacterial lipopolysaccharide (LPS) is accompanied by the secretion of type I interferons (IFNs) which can act in an autocrine manner. We examined the role of type I IFNs in macrophage responses to LPS using bone marrow-derived macrophages (BMM) from IFNAR1-/- mice, which lack a component of the type I IFN receptor and do not respond to type I IFNs. We found that, unlike wild-type (WT) BMM, LPS-treated IFNAR1-/- cells failed to produce nitric oxide (NO), or express inducible NO synthase (iNOS), indicating that type I IFNs are essential for all LPS-stimulated NO production in BMM. Exogenously added type II IFN (IFNgamma) rescued these responses in LPS-treated IFNAR1-/- BMM. In contrast to effects on NO, type I IFNs negatively regulated respiratory burst activity in LPS-primed BMM. We also found that while type I IFNs mediated the anti-proliferative effects of lower concentrations of LPS, at higher concentrations LPS acted in a type I IFNs-independent manner. Finally, we report that type I IFNs are a survival factor for BMM. Despite this, the ability of LPS to also prevent apoptosis in BMM was independent of type I IFNs. These findings highlight the diverse roles of type I IFNs in mediating LPS-stimulated macrophage responses. Copyright 2000 Academic Press.
机译:细菌脂多糖(LPS)对巨噬细胞的激活伴随着I型干扰素(IFNs)的分泌,它们可以自分泌的方式起作用。我们使用来自IFNAR1-/-小鼠的骨髓衍生巨噬细胞(BMM),检查了I型IFN在巨噬细胞对LPS的反应中的作用,该小鼠缺乏I型IFN受体的成分且对I型IFN无反应。我们发现,与野生型(WT)BMM不同,经LPS处理的IFNAR1-/-细胞无法产生一氧化氮(NO)或表达诱导型NO合酶(iNOS),这表明I型干扰素对于所有LPS-刺激了BMM中NO的产生。外源添加的II型IFN(IFNγ)在LPS处理的IFNAR1-/-BMM中挽救了这些反应。与对NO的影响相反,I型IFN在LPS引发的BMM中负调控呼吸爆发活性。我们还发现,虽然I型干扰素介导了较低浓度LPS的抗增殖作用,但在较高浓度下LPS却以I型干扰素非依赖性的方式起作用。最后,我们报告I型干扰素是BMM的生存因素。尽管如此,LPS还可阻止BMM凋亡,这与I型IFN无关。这些发现突出了I型IFN在介导LPS刺激的巨噬细胞应答中的不同作用。版权所有2000学术出版社。

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