ODC1 inhibits the inflammatory response and ROS-induced apoptosis in macrophages
ODC1 inhibits the inflammatory response and ROS-induced apoptosis in macrophages
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ODC1 抑制巨噬细胞的炎症反应和 ROS 诱导的细胞凋亡。
DOI：
10.1016/j.bbrc.2018.09.023
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发表时间：
2018-10-12
影响因子：
3.1
通讯作者：
Xiong, Sidong
中科院分区：
文献类型：
--
作者：
Jiang, Fang;Gao, Yue;Xiong, Sidong
巨噬细胞活化在先天免疫反应中起着关键作用。鸟氨酸脱羧酶（ODC1）将L - 鸟氨酸代谢为多胺，是多胺代谢中的限速酶，据报道多胺参与细胞分化、增殖和迁移。然而，ODC1在免疫细胞尤其是巨噬细胞中的功能及其潜在分子机制仍不明确。本研究揭示了ODC1在巨噬细胞中与脂多糖（LPS）、卡介苗（BCG）或四氯化碳（CCI4）诱导的炎症反应相关的潜在功能及机制。我们发现，LPS刺激后巨噬细胞中ODC1显著上调，且分别用LPS、BCG和CC14刺激时，ODC1对巨噬细胞促炎细胞因子分泌具有特异性抑制作用，这表明其作为炎症反应的一个共同调控元件发挥作用。对核因子 - κB和丝裂原活化蛋白激酶进行蛋白质免疫印迹分析显示，巨噬细胞中ODC1过表达后，多种转录因子的磷酸化受到显著抑制。此外，ODC1抑制活性氧诱导的和半胱天冬酶依赖的细胞凋亡，表现为ODC1上调后半胱天冬酶 - 3和 - 9表达降低。这些研究结果表明，ODC1参与减轻巨噬细胞受刺激后的炎症反应，使其成为炎症性疾病的一个潜在治疗靶点。（C）2018爱思唯尔公司。保留所有权利。
Macrophage activation plays a critical role in the innate immune response. Ornithine decarboxylase (ODC1) metabolizes L-ornithine to polyamines and is the rate-limiting enzyme involved in the metabolism of polyamines, which are reportedly involved in cell differentiation, proliferation, and migration. However, the function of ODC1 in immune cells and especially in macrophages, as well as its underlying molecular mechanism, remains unclear. This study revealed the potential ODC1 function and mechanism associated with the lipopolysaccharide (LPS)-, Bacillus Calmette Guerin (BCG)-, or carbon tetrachloride (CCI4)-induced inflammatory response in macrophages. We found significant upregulation of ODC1 in macrophages following LPS simulation and ODC1-specific suppression of proinflammatory cytokine secretion from macrophages upon stimulation with LPS, BCG and CC14, respectively, suggesting a role as a common control element of the inflammatory response. Western blotting for nuclear factor-kappa B and mitogen-activated protein kinases revealed significant inhibition of phosphorylation of multiple transcription factors following ODC1 overexpression in macrophages. Moreover, ODC1 inhibited reactive oxygen species-induced and caspase-dependent apoptosis highlighted by decreased caspase-3 and -9 expression following ODD upregulation. These findings indicated that ODC1 was involved in attenuating the inflammatory response upon stimulation of macrophages, making it a potential therapeutic target for inflammatory diseases. (C) 2018 Elsevier Inc. All rights reserved.