细胞质型磷脂酶 A2 起始的脂质介质途径诱导巨噬细胞自噬。
A cytosolic phospholipase A2-initiated lipid mediator pathway induces autophagy in macrophages.
机构信息
Critical Care Medicine Department, Clinical Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
J Immunol. 2011 Nov 15;187(10):5286-92. doi: 10.4049/jimmunol.1004004. Epub 2011 Oct 14.
Abstract
Autophagy delivers cytoplasmic constituents to autophagosomes and is involved in innate and adaptive immunity. Cytosolic phospholipase (cPLA(2))-initiated proinflammatory lipid mediator pathways play a critical role in host defense and inflammation. The crosstalk between the two pathways remains unclear. In this study, we report that cPLA(2) and its metabolite lipid mediators induced autophagy in the RAW246.7 macrophage cell line and in primary monocytes. IFN-γ-triggered autophagy involves activation of cPLA(2). Cysteinyl leukotrienes D(4) and E(4) and PGD(2) also induced these effects. The autophagy is independent of changes in mTOR or autophagic flux. cPLA(2) and lipid mediator-induced autophagy is ATG5 dependent. These data suggest that lipid mediators play a role in the regulation of autophagy, demonstrating a connection between the two seemingly separate innate immune responses, induction of autophagy and lipid mediator generation.
摘要
自噬将细胞质成分输送到自噬体中，并参与先天和适应性免疫。胞质型磷脂酶（cPLA（2））引发的促炎脂质介质途径在宿主防御和炎症中起着关键作用。这两种途径之间的串扰尚不清楚。在这项研究中，我们报告 cPLA（2）及其代谢脂质介质在 RAW246.7 巨噬细胞系和原代单核细胞中诱导自噬。IFN-γ 触发的自噬涉及 cPLA（2）的激活。半胱氨酰白三烯 D（4）和 E（4）和 PGD（2）也诱导了这些作用。自噬不依赖于 mTOR 或自噬通量的变化。cPLA（2）和脂质介质诱导的自噬依赖于 ATG5。这些数据表明脂质介质在自噬的调节中起作用，证明了两种看似独立的先天免疫反应（诱导自噬和脂质介质生成）之间的联系。
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