携带 CCL22 miRNA 的重组鼠伤寒沙门氏菌对小鼠特应性皮炎样皮肤的治疗作用。
Therapeutic effects of recombinant Salmonella typhimurium harboring CCL22 miRNA on atopic dermatitis-like skin in mice.
机构信息
Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
出版信息
Exp Mol Med. 2011 Feb 28;43(2):63-70. doi: 10.3858/emm.2011.43.2.008.
Abstract
Th-2-biased immune responses are known to play a key role in the pathogenesis of atopic dermatitis. In particular, the macrophage-derived chemokine CCL22 is directly implicated in Th-2-associated skin inflammatory reactions, and its levels are significantly elevated in serum and are correlated with disease severity in atopic dermatitis. In this study, we tested the development of genetic therapeutic options to treat atopic dermatitis using bacteria expressing miRNA. We constructed a recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The CCL22 gene was downregulated with CCL22 miRNA in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, interleukin-4 was inhibited and interferon-g was induced after treatments with ST-miRCCL22. Furthermore, CCL22 levels were suppressed in the atopic mice treated with ST-miRCCL22. These results suggest that ST-miRCCL22 may be an effective genetic agent for treating atopic dermatitis.
摘要
Th2 偏向性免疫应答被认为在特应性皮炎的发病机制中起关键作用。特别是，巨噬细胞衍生的趋化因子 CCL22 直接参与 Th2 相关的皮肤炎症反应，其水平在血清中显著升高，并与特应性皮炎的疾病严重程度相关。在这项研究中，我们测试了使用表达 miRNA 的细菌来开发治疗特应性皮炎的基因治疗选择。我们构建了表达 CCL22 miRNA 的鼠伤寒沙门氏菌重组菌株（ST-miRCCL22），用于体内敲低 CCL22。CCL22 基因在激活的淋巴细胞中被 CCL22 miRNA 下调。在具有类似于特应性皮炎的皮肤疾病的小鼠中，用 ST-miRCCL22 治疗后，白细胞介素-4 被抑制，干扰素-γ被诱导。此外，用 ST-miRCCL22 治疗的特应性小鼠中 CCL22 水平受到抑制。这些结果表明 ST-miRCCL22 可能是治疗特应性皮炎的有效遗传药物。
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