CpG ODN activates NO and iNOS production in mouse macrophage cell line (RAW 264•7)
CpG ODN activates NO and iNOS production in mouse macrophage cell line (RAW 264•7)
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DOI：
10.1046/j.1365-2249.2002.01866.x
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发表时间：
2002-06-01
影响因子：
4.6
通讯作者：
Sirisinha, S
中科院分区：
文献类型：
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作者：
Utaisincharoen, P;Anuntagool, N;Sirisinha, S
合成的含CpG的寡脱氧核苷酸（CpG ODN）被认为具有激活细胞产生几种细胞因子（如IL-12和TNF-α）的能力。在本研究中，我们已经证明，CpG ODN 1826，其免疫刺激活性在小鼠系统中已知的，本身可以诱导一氧化氮（NO）和诱导型一氧化氮合酶（iNOS）从小鼠巨噬细胞系（RAW 264.7）的生产。抗TNF-α的中和抗体不能抑制CpG ODN 1826激活的巨噬细胞产生NO或iNOS，这表明尽管TNF-α也由CpG ODN激活的巨噬细胞产生，但iNOS的产生不是通过TNF-α介导的。虽然CpG ODN 1826和脂多糖（LPS）都能够刺激NO和iNOS的产生，但CpG ODN 1826活化的巨噬细胞最大产生NO和iNOS所需的暴露时间显著长于用LPS活化的巨噬细胞。这些结果可能是由于NF-κ B易位的延迟，如IkappaB α降解的延迟所示。此外，氯喹消除了用CpG ODN 1826处理的细胞而不是用LPS处理的细胞的NO和iNOS产生的事实表明，从用CpG ODN（1826）刺激的细胞诱导NO和iNOS产生也需要内体成熟/酸化。
Synthetic CpG containing oligodeoxynucleotide (CpG ODN) is recognized for its ability to activate cells to produce several cytokines, such as IL-12 and TNF-alpha. In the present study we have demonstrated that CpG ODN 1826, known for its immunostimulatory activity in the mouse system could, by itself, induce nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production from mouse macrophage cell line (RAW 264.7). Neutralizing antibody against TNF-alpha was not able to inhibit NO or iNOS production from the CpG ODN 1826-activated macrophages, suggesting that although the TNF-alpha was also produced by CpG ODN-activated macrophages, the production of iNOS was not mediated through TNF-alpha. Although both CpG ODN 1826 and lipopolysaccharide (LPS) were able to stimulate NO and iNOS production, the exposure time required for maximum production of NO and iNOS for the CpG ODN 1826-activated macrophages was significantly longer than those activated with LPS. These results were due probably to a delay of NF-kappaB translocation, as indicated by the delay of IkappaBalpha degradation. Moreover, the fact that chloroquine abolished NO and iNOS production from the cells treated with CpG ODN 1826 but not from those treated with LPS suggested that the induction of NO and iNOS production from the cells stimulated with CpG ODN (1826) also required endosomal maturation/acidification.