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刺激性和抑制性DNA基序对宿主炎性关节炎易感性的影响。

Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis.

作者信息

Zeuner Rainald A, Verthelyi Daniela, Gursel Mayda, Ishii Ken J, Klinman Dennis M

机构信息

II Medical Clinic, University of Kiel, Kiel, Germany.

出版信息

Arthritis Rheum. 2003 Jun;48(6):1701-7. doi: 10.1002/art.11035.

DOI:10.1002/art.11035
PMID:12794839
Abstract

OBJECTIVE

To examine whether systemic administration of immunostimulatory and immunosuppressive oligodeoxynucleotides (ODNs) alter host susceptibility to inflammatory arthritis.

METHODS

Normal BALB/c mice were treated systemically with CpG ODNs or suppressive ODNs, and then challenged intraarticularly with CpG DNA. The onset and magnitude of the resulting inflammatory response was monitored.

RESULTS

Systemic delivery of CpG ODNs significantly increased susceptibility to local inflammation, whereas systemic treatment with suppressive ODNs reduced this susceptibility. CD11c+ cells played a key role in mediating host sensitivity to arthritis. These cells were the dominant source of tumor necrosis factor alpha production in CpG-stimulated animals and transferred resistance to arthritis from mice treated with suppressive ODNs.

CONCLUSION

Systemic exposure to immunostimulatory and immunosuppressive DNA influences host susceptibility to local inflammatory challenge. Current findings raise the possibility that suppressive ODNs may be useful in the prevention/treatment of proinflammatory diseases.

摘要

目的

研究免疫刺激性和免疫抑制性寡脱氧核苷酸(ODN)的全身给药是否会改变宿主对炎性关节炎的易感性。

方法

对正常BALB/c小鼠进行CpG ODN或抑制性ODN的全身治疗,然后关节内注射CpG DNA进行攻击。监测由此产生的炎症反应的发作和程度。

结果

全身递送CpG ODN显著增加了对局部炎症的易感性,而用抑制性ODN进行全身治疗则降低了这种易感性。CD11c+细胞在介导宿主对关节炎的敏感性中起关键作用。这些细胞是CpG刺激动物中肿瘤坏死因子α产生的主要来源,并将对关节炎的抗性从用抑制性ODN治疗的小鼠中转移过来。

结论

全身暴露于免疫刺激性和免疫抑制性DNA会影响宿主对局部炎症攻击的易感性。目前的研究结果提出了抑制性ODN可能有助于预防/治疗促炎性疾病的可能性。

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