Effect of suppressive sequences to inflammatory response induced by bacterial DNA CpG motif - a basic research on SIRS therapy.

CpG基序经常出现在细菌DNA中，被哺乳动物免疫系统识别为对宿主的危险信号并诱导免疫反应。哺乳动物DNA抑制cpg诱导的免疫反应。基于观察，Yamada等和Klieg等独立设计了抑制序列。他们广泛研究了这种抑制的性质，将新型抑制序列的治疗应用纳入范围。具有抑制序列的寡脱氧核苷酸（ODN）在小鼠RAW细胞中以剂量依赖的方式抑制CpG基序产生IL-6和IL-12。抑制ODN也能抑制RPMI 8227人B细胞株的IgM产生、增殖以及IL-6和IL-12的产生。体内研究表明，抑制性ODN显著抑制cpg诱导的肺部炎症，包括促炎细胞因子TNF-、IL-6趋化因子MIP-2和KC的产生，以及中性粒细胞向肺泡间隙的动员，Yamada等报道。NO是肺部炎症的重要气体介质。免疫荧光和RT-PCR结果显示，ODN减少了CpG基序诱导的iNOS表达。IL-12是将Th2免疫应答转换为Th1应答的关键细胞因子。因此，研究了抑制性ODN对IL-12产生的抑制作用。RT-PCR和荧光素酶检测IL-12 p40均显示，ODN抑制IL-12 mRNA的诱导。我们的观察证实了他们的发现。CpG基序引起多种疾病，如关节炎、脑膜炎、SLF和全身炎症反应综合征；先生们。本研究检测的抑制性ODN可能具有治疗效力。

CpG motifs that frequently appear in bacterial DNA are recognized by mammalian immune system as danger signal to the host and induce immune responses. Mammalian DNA suppresses CpG-induced immune responses. Based on the observation, Yamada et al. and Klieg et al. independently designed suppressive sequences. They extensively studied the nature of this suppression, taking therapeutic application of the novel suppressive sequences into scope. Oligodeoxynucleotides (ODN) with suppressive sequences inhibited IL-6 and IL-12 production by CpG motifs in a dose dependent manner in mouse RAW cells. IgM production, proliferation and the production of IL-6 and IL-12 were also inhibited by suppressive ODN in RPMI 8227 human B cell line in vitro. In vivo study showed that suppressive ODN significantly inhibited CpG-induced pulmonary inflammation, including the production of pro-inflammatory cytokines TNF-, IL-6 chemokines MIP-2 and KC, and mobilization of neutrophils into alveolar spaces as was reported by Yamada, et al. NO is important gaseous mediator of pulmonary inflammation. Immuno-fluorescence assay and RT-PCR showed ODN sup decreased iNOS expression induced by CpG motifs. IL-12 is a key cytokine that switches Th2 immune response to Th1 response. Inhibition of IL-12 production by suppressive ODN was thus studied. Both RT-PCR and luciferase assay for IL-12 p40 showed that suppressive ODN blocked IL-12 mRNA induction. Their findings were confirmed by our observations. CpG motifs cause several diseases such as arthritis, meningitis SLF, and systemic inflammatory response syndrome; SIRS. Suppressive ODN we tested in this study may have therapeutic potency.