Fiber-Nanotech Young Researcher Empowerment Center, Shinshu University, Minamiminowa 399-4598, Japan.
Biochem Biophys Res Commun. 2010 Mar 26;394(1):81-6. doi: 10.1016/j.bbrc.2010.02.110. Epub 2010 Feb 21.
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 24h 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-1alpha, IL-1beta and IL-18, are down-regulated after 24h 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.
我们之前报道了来自嗜热链球菌 ATCC19258 的 lacZ 基因的 CpG 寡脱氧核苷酸（ODN）MsST 具有很强的免疫刺激作用。在这里，我们表明在小鼠脾细胞和腹腔巨噬细胞中用 MsST 刺激 24 小时可强烈诱导白细胞介素（IL）-33 的表达，IL-33 是 IL-1 超家族中的一种细胞因子。在 MsST 刺激 24 小时后，其他 IL-1 超家族成员，包括 IL-1alpha、IL-1beta 和 IL-18，的表达水平下降。我们还发现 MsST 诱导的 IL-33 mRNA 表达受到抑制性 ODN A151 的抑制，A151 可以抑制 Toll 样受体 9（TLR9）介导的反应。这是首次报道 CpG ODN 可以诱导 IL-33 的表达。MsST 强烈诱导 IL-33 的表达表明，它可能是治疗炎症性疾病的潜在治疗性 ODN。嗜热链球菌中存在强 CpG ODN 也表明该细菌可能是开发新型生理功能食品的良好候选 starter 培养物。
