Immunostimulatory oligonucleotides inhibit colonic proinflammatory cytokine production in ulcerative colitis.
Immunostimulatory oligonucleotides inhibit colonic proinflammatory cytokine production in ulcerative colitis.
复制标题
免疫刺激寡核苷酸抑制溃疡性结肠炎中结肠促炎细胞因子的产生。
DOI：
10.1097/01.mib.0000217335.30689.77
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发表时间：
2006
影响因子：
4.9
通讯作者：
Raz,Eyal
中科院分区：
文献类型：
--
作者：
Rachmilewitz,Daniel;Karmeli,Fanny;Shteingart,Shimon;Lee,Jongdae;Takabayashi,Kenji;Raz,Eyal
背景：我们先前表明Toll样受体-9（TLR-9）配体可改善实验性结肠炎。在这项研究中，我们评估TLR-9配体对人类结肠mucosa.Materials和Methods的促炎细胞因子的产生的影响：结肠镜活检，从活动性溃疡性结肠炎（UC）患者和正常受试者。在存在或不存在不同类型的免疫刺激性（ISS）（CpG）-寡核苷酸（ODN）的情况下，将组织器官培养24小时。结果：在活动期UC中，炎症结肠粘膜产生的hTNF-α和hIL-1 β分别是正常结肠粘膜的7倍和3倍。B类CpG ODN抑制结肠TNF-α和IL-1β产生50%，而A类或C类ODN分别具有部分或无作用。一类新的基于多个TCG重复序列的ODN与B类ODN一样有效。这种抑制作用是由ISS-ODN孵育后前2小时内发生的IL-1β转录抑制引起的。结论：只有某些类别的ISS-ODNs抑制UC患者炎症结肠黏膜体外产生的增强的TNF-α和IL-1 β。ISS-ODN的作用是通过触发TLR-9介导的。这些结果表明ISS‐ ODN在UC中具有潜在的治疗价值。
Background: We previously showed that Toll‐like receptor‐9 (TLR‐9) ligands ameliorate experimental colitis. In this study, we evaluated the effect of TLR‐9 ligands on the generation of proinflammatory cytokines by human colonic mucosa.Materials and Methods: Colonoscopic biopsies were obtained from patients with active ulcerative colitis (UC) and from normal subjects. The tissue was organ cultured for 24 hours in the presence or absence of different types of immunostimulatory (ISS) (CpG)‐oligonucleotides (ODNs). Tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) levels in the medium were determined by enzyme‐linked immunosorbent assay.Results: In active UC, hTNF‐α and hIL‐1β generation by inflamed colonic mucosa is 7‐ and 3‐fold higher, respectively, than their generation by normal mucosa. Class B CpG ODNs inhibited colonic TNF‐α and IL‐1β generation by 50%, whereas class A or C ODNs had a partial or no effect, respectively. A novel class of ODNs that is based on multiple TCG repeats was as effective as class B ODNs. This inhibition resulted from the transcriptional suppression of IL‐1β that occurred within the first 2 hours after ISS‐ODN incubation. The addition of chloroquine abolished the inhibitory effects of ISS‐ODNs on colonic TNF‐α and IL‐1β generation.Conclusions: Only certain classes of ISS‐ODNs inhibit the enhanced TNF‐α and IL‐1β generated ex vivo by inflamed colonic mucosa of patients with UC. The effect of ISS‐ODNs is mediated by triggering of TLR‐9. These results suggest a potential therapeutic value for ISS‐ODNs in UC.