博来霉素对巨噬细胞杀瘤活性的恢复与携带KDH-8肝癌细胞的大鼠体内转化生长因子β产生的减少相关。
Restoration of macrophage tumoricidal activity by bleomycin correlates with the decreased production of transforming growth factor beta in rats bearing KDH-8 hepatoma cells.
作者信息
Yuan L, Kobayashi M, Kuramitsu Y, Li Y, Matsushita K, Hosokawa M
机构信息
Laboratory of Pathology, Hokkaido University School of Medicine, Sapparo, Japan.
出版信息
Cancer Immunol Immunother. 1997 Oct;45(2):71-6. doi: 10.1007/s002620050404.
To explore the mechanisms of immuno-modulatory activities of bleomycin, we investigated interferon gamma (IFN gamma) mRNA expression, tumor necrosis factor alpha (TNF alpha) production, nitric oxide (NO) production and macrophage tumoricidal activities in rats bearing KDH-8 hepatoma cells, which secreted a large amount of transforming growth factor beta (TGF beta), and these processes in KDH-8 tumor-bearing rats treated with bleomycin. We found that IFN gamma mRNA expression, TNF alpha production, NO production and macrophage cytotoxic activities were lower in the KDH-8-bearing rats than in normal rats. On the other hand, low-dose bleomycin restored the macrophage cytotoxic activities, NO production, IFN gamma mRNA expression and TNF alpha production in the KDH-8-bearing rats. In vitro experiments showed that KDH-8-derived TGF beta decreased the IFN gamma mRNA expression and TNF alpha production in splenocytes, and NO production in peritoneal macrophages. These results suggest that low-dose bleomycin restored the cytokine production and macrophage tumoricidal activities in the KDH-8-bearing rats by decreasing KDH-8-derived TGF beta.
为探究博来霉素免疫调节活性的机制，我们研究了携带KDH - 8肝癌细胞的大鼠（该细胞分泌大量转化生长因子β（TGFβ））中的干扰素γ（IFNγ）mRNA表达、肿瘤坏死因子α（TNFα）产生、一氧化氮（NO）产生以及巨噬细胞杀肿瘤活性，以及用博来霉素处理的携带KDH - 8肿瘤大鼠中的上述过程。我们发现，携带KDH - 8的大鼠中IFNγ mRNA表达、TNFα产生、NO产生以及巨噬细胞细胞毒性活性均低于正常大鼠。另一方面，低剂量博来霉素恢复了携带KDH - 8的大鼠中的巨噬细胞细胞毒性活性、NO产生、IFNγ mRNA表达和TNFα产生。体外实验表明，KDH - 8来源的TGFβ降低了脾细胞中IFNγ mRNA表达和TNFα产生，以及腹膜巨噬细胞中的NO产生。这些结果表明，低剂量博来霉素通过减少KDH - 8来源的TGFβ恢复了携带KDH - 8的大鼠中的细胞因子产生和巨噬细胞杀肿瘤活性。
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