Keratinocyte gene therapy for systemic diseases. Circulating interleukin 10 released from gene-transferred keratinocytes inhibits contact hypersensitivity at distant areas of the skin.

Keratinocyte gene therapy for systemic diseases. Circulating interleukin 10 released from gene-transferred keratinocytes inhibits contact hypersensitivity at distant areas of the skin.
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角质形成细胞基因治疗全身性疾病。

DOI:
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发表时间:
1998
影响因子:
15.9
通讯作者:
Isao Hashimoto
Isao Hashimoto
中科院分区:
医学1区
文献类型:
--
作者:
Xianmin Meng;D. Sawamura;K. Tamai;K. Hanada;H. Ishida;Isao Hashimoto

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本研究检查了转导角质形成细胞释放的循环基因产物人白细胞介素 10 (IL-10) 的全身效应。 IL-10是一种抗炎细胞因子,对接触性超敏反应(CHS)有抑制作用。构建人IL-10表达载体(phIL-10)并将其注射到无毛大鼠的背部皮肤中。分别通过逆转录酶聚合酶链反应和免疫组化染色检测IL-10 mRNA和蛋白的局部表达。酶联免疫吸附测定显示,局部角质形成细胞和循环中IL-10的量随着phIL-10转移剂量的增加而增加。为了确定循环IL-10是否可以抑制远距离皮肤区域的CHS效应期,在对耳朵进行攻击之前,将不同剂量的phIL-10注射到致敏大鼠的背部皮肤中。我们的结果表明,phIL-10处理的大鼠耳朵肿胀程度明显低于阴性对照动物。这些结果表明,转导的角质形成细胞释放的 IL-10 可以进入血流并在皮肤的远处区域产生生物效应。这项研究表明,使用角质形成细胞基因疗法治疗全身性疾病是可能的。
This study has examined the systemic effects of a circulating gene product, human interleukin 10 (IL-10), released from transduced keratinocytes. IL-10 is an anti-inflammatory cytokine which has an inhibitory effect on contact hypersensitivity (CHS). An expression vector (phIL-10) was constructed for human IL-10 and was injected into the dorsal skin of hairless rats. Local expression of IL-10 mRNA and protein was detected by reverse-transcriptase polymerase chain reaction and immunohistochemical staining, respectively. Enzyme-linked immunosorbent assay showed that the amount of IL-10 in the local keratinocytes and in the circulation increased with the dose of phIL-10 transferred. To determine whether circulating IL-10 could inhibit the effector phase of CHS at a distant area of the skin, various doses of phIL-10 were injected into the dorsal skin of sensitized rats before challenge on the ears. Our results showed that the degree of swelling of the ears of phIL-10- treated rats was significantly lower than that in the negative control animals. These results suggest that IL-10 released from transduced keratinocytes can enter the bloodstream and cause biological effects at distant areas of the skin. This study demonstrates that it may be possible to treat systemic disease using keratinocyte gene therapy.
来自常见变异型免疫缺陷患者的活化 B 细胞会增殖并合成免疫球蛋白。
DOI: 10.1172/jci116701
发表时间: 1993
期刊: The Journal of clinical investigation
影响因子: --
作者:
Nonoyama,S;Farrington,M;Ishida,H;Howard,M;Ochs,HD
通讯作者: Ochs,HD
DOI: 10.1093/hmg/1.6.363
发表时间: 1992-01-01
影响因子: 3.5
作者:
Wolff, Jon A.;Ludtke, James J.;Jani, Agnes
通讯作者: Jani, Agnes
表皮:基因治疗的一个有吸引力的靶组织。
DOI: 10.1111/1523-1747.ep12399070
发表时间: 1994
期刊: The Journal of investigative dermatology
影响因子: --
作者:
Greenhalgh,DA;Rothnagel,JA;Roop,DR
通讯作者: Roop,DR
通过肌内注射复制缺陷型腺病毒,将生理水平的重组促红细胞生成素稳定输送至体循环。
DOI: 10.1073/pnas.91.24.11557
发表时间: 1994
影响因子: 11.1
作者:
Tripathy,SK;Goldwasser,E;Lu,MM;Barr,E;Leiden,JM
通讯作者: Leiden,JM