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首页> 外文期刊>Journal of Cellular Physiology >Interleukin (IL)-12 mediates the anti-osteoclastogenic activity of CpG-oligodeoxynucleotides.
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Interleukin (IL)-12 mediates the anti-osteoclastogenic activity of CpG-oligodeoxynucleotides.

机译：白介素(IL) -12年协调anti-osteoclastogenic活动CpG-oligodeoxynucleotides。

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Bacterial DNA activates the innate immune system via interactions with Toll-like receptor 9 (TLR9). This receptor recognizes CpG-oligodeoxynucleotides (CpG-ODNs) mimicking the CpG dinucleotides in certain sequence contexts characterizing this DNA. Most studies have shown increased osteoclast differentiation by TLR ligands. We found that activation of TLRs (specifically TLR4 and TLR9) in early osteoclast precursors results in inhibition of receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast differentiation. Our objective is to identify the mechanism leading to this inhibitory effect of a TLR ligand. Since both RANKL-RANK and CpG-ODN-TLR9 interactions result in NF-kappaB activation, p38 and ERK phosphorylation, and TNF-alpha synthesis (all implicated in osteoclastogenesis), we hypothesized that CpG-ODN (but not RANKL) in addition induces the synthesis of an anti-osteoclastogenic factor. Control osteoclast precursors, and cells treated with RANKL, CpG-ODN, or their combination were studied using DNA arrays (GEArray Q Series Mouse NF-kappaB Signaling Pathway Gene Array, MM-016, SuperArray). We found a marked increase in the mRNA levels of the osteoclastogenesis inhibitor interleukin-12 (IL-12) in osteoclast precursors treated with CpG-ODN and CpG-ODN + RANKL. Northern and Western analyses, together with ELISA, confirmed the DNA array studies. In correlation with these findings, IL-12 inhibited RANKL-induced osteoclast differentiation and specific anti-IL-12-antibodies inhibited the anti-osteoclastogenic effect of CpG-ODN. In conclusion, activation of TLR9 by its ligand, CpG-ODN, results in synthesis and release of IL-12 opposing RANKL-induced osteoclast differentiation.
机译：细菌的DNA激活先天免疫系统通过与toll样受体相互作用9(TLR9识别)。CpG-oligodeoxynucleotides (CpG-ODNs)模仿中央人民政府在某些序列二核苷酸上下文描述DNA。显示增加破骨细胞分化TLR配体。早期破骨细胞(尤其是TLR4和TLR9识别)在抑制受体前体结果激活全身的NF-kappaB配体(RANKL)破骨细胞分化。识别导致这种抑制机制TLR配体的影响。导致NF-kappaB CpG-ODN-TLR9交互p38和ERK的磷酸化,激活tnf合成(所有涉及osteoclastogenesis),我们假设CpG-ODN(但不是RANKL)此外诱导合成anti-osteoclastogenic的因素。破骨细胞前体,细胞治疗RANKL CpG-ODN,或它们的组合进行了研究使用DNA阵列(GEArray Q系列鼠标NF-kappaB信号通路基因阵列,mm - 016,SuperArray)。osteoclastogenesis抑制剂的mRNA水平在破骨细胞前体interleukin-12 (il - 12)接受CpG-ODN和CpG-ODN + RANKL。北部和西部的分析,结合ELISA,证实了DNA阵列的研究。相关性与这些发现,il - 12抑制RANKL-induced破骨细胞分化和具体anti-IL-12-antibodies抑制anti-osteoclastogenic CpG-ODN的效果。结论,激活TLR9识别的配体,CpG-ODN,结果的合成和释放白介素反对RANKL-induced破骨细胞分化。

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