CpG oligodeoxynucleotides induce strong up-regulation of interleukin 33 via Toll-like receptor 9

CpG oligodeoxynucleotides induce strong up-regulation of interleukin 33 via Toll-like receptor 9
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DOI:
10.1016/j.bbrc.2010.02.110
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发表时间:
2010-03-26
影响因子:
3.1
通讯作者:
Kitazawa, Haruki
Kitazawa, Haruki
中科院分区:
生物学4区
文献类型:
--
作者:
Shimosato, Takeshi;Fujimoto, Megumi;Kitazawa, Haruki

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我们先前报道了来自链球菌(S.)lacZ基因的CpG寡脱氧核苷酸(MsST)的强免疫刺激作用。嗜热菌ATCC 19258。在这里,我们表明,24小时的刺激与MsST在小鼠脾细胞和腹腔巨噬细胞强烈诱导白细胞介素(IL)-33,IL-1超家族中的细胞因子的表达。其他IL-1超家族成员,包括IL-1 α、IL-1 β和IL-18,在MsST刺激24小时后下调。我们还发现MsST诱导的IL-33 mRNA表达被抑制性ODN A151抑制,其可以抑制Toll样受体9(TLR 9)介导的反应。这是第一份表明CpG ODN可以诱导IL-33的报道。MsST对IL-33的强诱导作用提示其可能是一种潜在的治疗炎症性疾病的ODN。S.嗜热菌的研究还表明,该细菌可能是开发新的生理功能食品的发酵剂的良好候选者。(C)2010年爱思唯尔公司All rights reserved.
We previously reported the strong immunostimulatory effects of a CpG oligodeoxynucleotide (ODN), designated MsST, from the lacZ gene of Streptococcus (S.) thermophilus ATCC19258. Here we show that 24 h of stimulation with MsST in mouse splenocytes and peritoneal macrophages strongly induces expression of interleukin (IL)-33, a cytokine in the IL-1 superfamily. Other IL-1 superfamily members, including IL-1 alpha, IL-1 beta and IL-18, are down-regulated after 24 h of stimulation of MsST. We also found that MsST-induced IL-33 mRNA expression is inhibited by the suppressive ODN A151, which can inhibit Toll-like receptor 9 (TLR9)-mediated responses. This is the first report to show that IL-33 can be induced by CpG ODNs. The strong induction of IL-33 by MsST suggests that it may be a potential therapeutic ODN for the treatment of inflammatory disease. The presence of a strong CpG ODN in S. thermophilus also suggests that the bacterium may be a good candidate as a starter culture for the development of new physiologically functional foods. (C) 2010 Elsevier Inc. All rights reserved.