Canine interleukin-18 induces apoptosis and enhances Fas ligand mRNA expression in a canine carcinoma cell line.
Canine interleukin-18 induces apoptosis and enhances Fas ligand mRNA expression in a canine carcinoma cell line.
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作者：
F. Okano;K. Yamada
碘化丙啶染色后，通过电泳 DNA 分离和流式细胞术测定，重组犬白细胞介素 18 (IL-18) 在体外诱导源自犬乳腺肿瘤组织的犬癌细胞系凋亡。为了研究 Fas 配体 (FasL) 在细胞系上的表达，我们从犬淋巴细胞中克隆了犬 Fas 配体 (FasL) cDNA 的部分序列。通过 RT-PCR 分析，我们发现该细胞系表达 FasL mRNA，并且通过犬 IL-18 处理而增强，并通过添加犬 IL-12 进一步增强。用重组犬IL-18治疗导致移植到scid小鼠中的细胞系完全消退。这种抗肿瘤活性不会被抗小鼠 IFN-γ 和抗去唾液酸 GM1 抗体阻断，表明肿瘤消退不依赖于 IFN-γ 或宿主的 NK 细胞。由于犬IL-18与小鼠宿主细胞没有交叉反应性，这些结果表明犬IL-18可能能够通过诱导细胞凋亡直接杀死乳腺癌细胞。犬 IL-18 应该被证明是一种有用的抗癌剂。
Recombinant canine interleukin-18 (IL-18) induced apoptosis in vitro in a canine cancer cell line derived from canine mammary gland tumor tissue as determined by electrophoretical DNA separation and flow cytometry after propidium iodine staining. To investigate Fas ligand (FasL) expression on the cell line, we cloned the partial sequence of canine Fas Ligand (FasL) cDNA from canine lymphocytes. We found, by RT-PCR analyses, that the cell line expressed FasL mRNA and it was augmented by treatment with canine IL-18 and further enhanced by addition of canine IL-12. Treatment with recombinant canine IL-18 resulted in complete regression of the cell line transplanted into scid mice. This anti-tumor activity was not blocked by anti-mouse IFN-gamma and anti-asialo GM1 antibody, suggesting that the tumor regression was not dependent on IFN-gamma or NK cells of the host. Because there is no cross-reactivity of canine IL-18 with mouse host cells, these results suggested that canine IL-18 may be able to directly kill the breast cancer cells by inducing apoptosis. Canine IL-18 should prove useful as an anti-cancer agent.