Effect of suppressive oligodeoxynucleotides on the development of inflammation-induced papillomas.
Effect of suppressive oligodeoxynucleotides on the development of inflammation-induced papillomas.
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DOI：
10.1158/1940-6207.capr-10-0290
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Klinman DM
中科院分区：
文献类型：
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作者：
Ikeuchi H;Kinjo T;Klinman DM
在公认的DMBA/TPA皮肤癌变模型中，炎症有助于乳头状瘤和鳞状细胞癌的发展。含有重复TTAGGG基序的合成寡核苷酸(ODN)已被证明可以阻断自身免疫、肺炎和休克小鼠模型中的有害炎症反应。这项工作检查了抑制性(Sup)ODN治疗是否可以干扰DMBA/TPA诱导的炎症，从而减少乳头状瘤的形成。结果表明，Sup ODN可抑制TPA依赖的皮肤增生、水肿和白细胞浸润。Sup ODN还抑制癌前趋化因子和其他炎症标志基因的上调，包括CXCL2、CCL2、COX-2和ODC。最重要的是，Sup ODN以剂量和序列依赖的方式减少乳头状瘤的形成。这些发现表明，Sup ODN可能提供了一种新的方法来预防炎症和相关的肿瘤发生。
Inflammation contributes to the development of papillomas and squamous cell carcinomas in the well established DMBA/TPA model of skin carcinogenesis. Synthetic oligonucleotides (ODN) containing repetitive TTAGGG motifs have been shown to block deleterious inflammatory reactions in murine models of autoimmunity, pneumonitis and shock. This work examines whether treatment with suppressive (Sup) ODN can interfere with DMBA/TPA induced inflammation, thereby reducing papilloma formation. Results indicate that Sup ODN block TPA-dependent skin hyperplasia, edema and leukocytic infiltration. Sup ODN also inhibit the up-regulation of genes encoding pro-oncogenic chemokines and other markers of inflammation including CXCL2, CCL2, COX-2 and ODC. Of greatest import, Sup ODN reduce papilloma formation in a dose and sequence dependent manner. These findings suggest that Sup ODN may provide a novel means of preventing inflammation and associated oncogenesis.