丝裂霉素-C处理胰岛异种移植后，转化生长因子-β信号增强。

Transforming growth factor-beta signaling is enhanced following mitomycin-C treatment of islet xenograft.

作者信息

Ise K, Sato Y, Matsuyama S, Gunji T, Ishii S, Yamashita M, Kanazawa Y, Gotoh M

机构信息

Department of Surgery, Fukushima Medical University, Fukushima, Japan.

出版信息

Transplant Proc. 2004 May;36(4):1183-5. doi: 10.1016/j.transproceed.2004.04.029.

DOI:10.1016/j.transproceed.2004.04.029

PMID:15194410

Abstract

Mitomycin-C (MMC) is categorized as an agent that causes genotoxic stress by triggering various intracellular signaling pathways. We have previously shown that MMC pretreatment of highly immunogenic crude islets leads to significant prolongation of graft survival in a rat-to-mouse model. In the present study, we examined whether TH1/TH2 cytokine, including the inflammatory cytokines interferon-gamma and interleukin (IL)-2, or the Th2 group, IL-4, IL-10, TNF-alpha, IL-1 beta, IL-6, GM-CSF, and transforming growth factor (TGF)-beta were up-regulated or down-regulated following MMC treatment of islets. We found changes in TGF-beta messenger RNA (mRNA) transcription as the only events among the measured cytokines. TGF-beta concentration was elevated in blebs formed under the kidney capsule, but not in the serum or ascites among animals given MMC-treated islets than in animals given untreated islets, suggesting local processes induced by MMC might inhibit xenograft rejection.

摘要

丝裂霉素-C（MMC）被归类为一种通过触发各种细胞内信号通路引起基因毒性应激的药物。我们之前已经表明，在大鼠到小鼠的模型中，用MMC预处理具有高度免疫原性的粗制胰岛可显著延长移植物存活时间。在本研究中，我们检测了在MMC处理胰岛后，包括炎性细胞因子干扰素-γ和白细胞介素（IL）-2在内的TH1/TH2细胞因子，或Th2组的IL-4、IL-10、TNF-α、IL-1β、IL-6、GM-CSF和转化生长因子（TGF）-β是上调还是下调。我们发现，在所检测的细胞因子中，TGF-β信使核糖核酸（mRNA）转录的变化是唯一的事件。在给予MMC处理胰岛的动物中，肾被膜下形成的水泡中TGF-β浓度升高，但血清或腹水中的TGF-β浓度并未升高，而给予未处理胰岛的动物则相反，这表明MMC诱导的局部过程可能抑制异种移植排斥反应。