Up-regulation of NOD1 and NOD2 through TLR4 and TNF-α in LPS-treated murine macrophages
Up-regulation of NOD1 and NOD2 through TLR4 and TNF-α in LPS-treated murine macrophages
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DOI：
10.1292/jvms.68.471
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发表时间：
2006-05-01
影响因子：
1.2
通讯作者：
Imakawa, K
中科院分区：
文献类型：
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作者：
Takahashi, Y;Isuzugawa, K;Imakawa, K
Nod1(Card4)和NOD2(Card15)被认为负责细胞质防御细菌入侵。以进一步了解它们在小鼠巨噬细胞中的表达是如何调节的。我们研究了不同内毒素、脂多糖、脂磷壁酸和肽聚糖刺激后NOD1和NOD2基因的表达。巨噬细胞RAW264.7在内毒素处理后2小时和8-12小时，NOD1和NOD2的mRNAs分别出现第一次和第二次升高。在脂多糖处理的RAW264.7细胞中，NOD1和NOD2mRNAs的增加在2小时后被使用核转录因子-kappaB抑制剂降低。咖啡酸苯乙酯。在RAW264.7细胞中，抗TLR4抗体可抑制脂多糖诱导的NOD1和NOD2mRNAs的增加，而在TLR4缺陷小鼠的腹腔巨噬细胞中则部分减少。更重要的是。促炎细胞因子可上调RAW264.7细胞NOD I和NOD2基因的表达。肿瘤坏死因子-α(TNF-α)、白介素1-β(IL-1β)或IL-6。在肿瘤坏死因子-α缺乏的巨噬细胞中，NOD分子的表达在12小时时最低，而在脂多糖处理的RAW264.7细胞中，NOD基因的第二次表达被抗肿瘤坏死因子-α抑制。但不包括抗IL-1β或抗IL-6抗体。这些观察结果提示，NOD对内毒素的即时反应可能是通过TLR信号途径激活了NF-kappa B，而NOD mRNAs的第二次升高可能是通过NF-kappa B-TLR产生的肿瘤坏死因子-α。和/或点头信号。
NOD1 (Card4) and NOD2 (Card15) are thought to be responsible for cytoplasmic defense against bacterial entry. To gain further knowledge about how their expressions are regulated in murine macrophages. we investigated the expression of NOD1 and NOD2 mRNAs after stimulation with various endotoxins, lipopolysaccharide, lipoteichoic acid and peptidoglycan. In macrophage RAW264.7 cells, the first and second rises in NOD1 and NOD2 mRNAs were observed at 2 hr and at 8-12 hr after endotoxin treatment. Increases in NOD1 and NOD2 mRNAs at 2 hr in lipopolysaccharide-treated RAW264.7 cells were reduced with the use of NF-kappa B inhibitor. caffeic acid phenetyl ester. In RAW264.7 cells, lipopolysaccharide-induced increases in NOD1 and NOD2 mRNAs were inhibited with anti-TLR4 antibody, and partially reduced in peritoneal macrophages obtained from TLR4-deficient mice. Furthermore. NOD I and NOD2 mRNA expressions in RAW264.7 cells were increased by the treatment with proinflammatory cytokines. tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or IL-6. In TNF-alpha deficient macrophages, the expression of NOD molecules was minimal at 12 hr, and the second rise in NOD mRNA seen in lipopolysaccharide-treated RAW264.7 cells was inhibited with anti-TNF-alpha. but not with anti-IL-1 beta or anti-IL-6 antibody. These observations suggest that immediate response of NODS to endotoxins could result from NF-kappa B activation via TLR signaling, whereas the second rise in NOD mRNAs might have resulted from TNF-alpha production possibly through NF-kappa B. TLR. and/or NOD signalings.