Inhibition by interleukin-18 of the growth of Dunn osteosarcoma cells.
Inhibition by interleukin-18 of the growth of Dunn osteosarcoma cells.
复制标题
DOI：
10.1089/107999004322917007
复制
发表时间：
2004-07
期刊：
影响因子：
--
通讯作者：
T. Okamoto;N. Yamada;T. Tsujimura;A. Sugihara;Y. Nishizawa;H. Ueda;S. Kashiwamura;H. Tsutsui;H. Futani;S. Maruo;H. Okamura;N. Terada
中科院分区：
文献类型：
--
作者：
T. Okamoto;N. Yamada;T. Tsujimura;A. Sugihara;Y. Nishizawa;H. Ueda;S. Kashiwamura;H. Tsutsui;H. Futani;S. Maruo;H. Okamura;N. Terada
为探讨白细胞介素18(IL-18)在骨肉瘤治疗中的作用，观察了IL-18对骨肉瘤细胞生长的影响。每日腹腔注射(Ip)注射小鼠重组IL-18(2微克/只)可抑制皮下移植的骨肉瘤细胞的生长。转化为同基因C3H小鼠。这种IL-18诱导的抑制不受抗asialo GM1血清处理的影响，后者可灭活自然杀伤(NK)细胞。但IL-18不能抑制DUNN骨肉瘤细胞移植到T淋巴细胞缺失的BALB/c裸鼠和Fas配体(FasL)缺失的C3HGLD/GLD小鼠体内。逆转录聚合酶链式反应(RT-PCR)检测到骨肉瘤细胞表达IL-18受体mRNA、MyD88 mRNA和Fas mRNA，但IL-18对骨肉瘤细胞的生长无明显抑制作用。另一方面，抗小鼠Fas抗体在体外对Dunn骨肉瘤细胞具有杀伤作用，且呈剂量依赖关系。此外，用IL-18处理C3H小鼠后，CD8(+)T淋巴细胞对Dunn骨肉瘤细胞的杀伤活性增强。提示IL-18可通过FasL-Fas系统增强CD8(+)T细胞的细胞毒活性，从而抑制骨肉瘤细胞的生长。
To examine the usefulness of interleukin-18 (IL-18) in the treatment of osteosarcomas, the effect of IL-18 on the growth of Dunn osteosarcoma cells was investigated. Daily intraperitoneal (i.p.) injection of mouse recombinant IL-18 (2 microg/mouse) suppressed the growth of Dunn osteosarcoma cells transplanted subcutaneously (s.c.) into syngeneic C3H mice. This IL-18-induced suppression was not affected by simultaneous treatment with anti-asialo GM1 serum, which inactivates natural killer (NK) cells. However, IL-18 failed to suppress the growth of Dunn osteosarcoma cells transplanted into BALB/c-nude mice devoid of T lymphocytes or C3H-gld/gld mice deficient in functional Fas ligand (FasL). IL-18 also failed to suppress the growth of Dunn osteosarcoma cells in vitro, although expression of IL-18 receptor mRNA and MyD88 mRNA as well as Fas mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). On the other hand, antimouse Fas antibody showed cytotoxicity against Dunn osteosarcoma cells in a dose-dependent manner in vitro. In addition, treatment of C3H mice with IL-18 enhanced the cytotoxic activity of CD8(+) T lymphocytes against Dunn osteosarcoma cells. These results indicate that IL-18 inhibits the growth of Dunn osteosarcoma cells in vivo by enhancing the cytotoxic activity of CD8(+) T lymphocytes through the FasL-Fas system.