白细胞介素-2/白细胞介素-18通过c-Jun氨基末端激酶（JNK）途径防止转化生长因子-β下调自然杀伤细胞中NKG2D的表达。
IL-2/IL-18 prevent the down-modulation of NKG2D by TGF-beta in NK cells via the c-Jun N-terminal kinase (JNK) pathway.
作者信息
Song Hyunkeun, Hur Dae Young, Kim Kyung-Eun, Park Hyunjeong, Kim Taesung, Kim Chul-Woo, Bang Saic, Cho Dae-Ho
机构信息
Department of Anatomy, Inje University, College of Medicine, Pusan 614-735, South Korea.
出版信息
Cell Immunol. 2006 Jul;242(1):39-45. doi: 10.1016/j.cellimm.2006.09.002. Epub 2006 Oct 27.
TGF-beta is known to play a major role for the reduced NKG2D expression seen in cancer patients. However, the mechanisms for reduced TGF-beta-induced down-regulation of NKG2D are unclear. In this study, we observed that IL-2/IL-18 increased the NKG2D expression in the TGF-beta treated NK cell line in a dose-dependent manner. Incubation with the JNK inhibitor SP600125 inhibited the NKG2D expression induced by IL-2/IL-18 in the TGF-beta treated human NK cell line. Moreover, the NK cytotoxicity assay showed that the reduced NK cytotoxicity by TGF-beta was recovered by IL-2/IL-18 treatment. The results indicate that IL-2/IL-18 strongly prevented the TGF-beta-induced NKG2D down-regulation in NK cells via the JNK pathway. Taken together, the protected expression of NKG2D by IL-2/IL-18 provides insight into the mechanism of NKG2D regulation and it also supplied useful information for creating a novel therapeutic approach to treat TGF-beta-secreting cancer cells.
已知转化生长因子β（TGF-β）在癌症患者中自然杀伤细胞2D（NKG2D）表达降低方面起主要作用。然而，TGF-β诱导NKG2D下调的机制尚不清楚。在本研究中，我们观察到白细胞介素2（IL-2）/白细胞介素18（IL-18）以剂量依赖的方式增加了经TGF-β处理的自然杀伤（NK）细胞系中NKG2D的表达。用应激活化蛋白激酶（JNK）抑制剂SP600125孵育可抑制经TGF-β处理的人NK细胞系中由IL-2/IL-18诱导的NKG2D表达。此外，NK细胞毒性试验表明，TGF-β降低的NK细胞毒性通过IL-2/IL-18处理得以恢复。结果表明，IL-2/IL-18通过JNK途径强烈阻止了TGF-β诱导的NK细胞中NKG2D下调。综上所述，IL-2/IL-18对NKG2D表达的保护作用为NKG2D调节机制提供了见解，也为开发治疗分泌TGF-β的癌细胞的新型治疗方法提供了有用信息。
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