DECREASE IN PHOSPHORYLATION OF ERK FOLLOWING DECREASED EXPRESSION OF NK CELL-ACTIVATING RECEPTORS IN HUMAN NK CELL LINE EXPOSED TO ASBESTOS
DECREASE IN PHOSPHORYLATION OF ERK FOLLOWING DECREASED EXPRESSION OF NK CELL-ACTIVATING RECEPTORS IN HUMAN NK CELL LINE EXPOSED TO ASBESTOS
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DOI：
10.1177/039463200902200403
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发表时间：
2009-10-01
影响因子：
3.5
通讯作者：
Otsuki, T.
中科院分区：
文献类型：
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作者：
Nishimura, Y.;Maeda, M.;Otsuki, T.
YT-CB5 与温石棉 B (CB) 石棉一起连续培养，显示出细胞毒性受损，NKG2D 和 2B4 NK 细胞激活受体的表达下降。在本研究中，通过 How 细胞术检测 YT-CB5 中细胞外信号调节激酶 (ERK) 的磷酸化，并与对照系 YT-Org 进行比较，该磷酸化已知可诱导许多 NK 细胞激活受体下游的脱颗粒。 YT-CB5 表现出由 K562 细胞识别诱导的 ERK1/2 磷酸化受损，这是 Src 家族激酶和磷酸肌醇 3-激酶介导的过程的下游。在抗 2B4 抗体存在的情况下与 K562 细胞一起孵育后，YT-CB5 也表现出 ERK1/2 磷酸化受损，其中 2134 的共刺激增强了 YT-CB5 中 ERK1/2 的磷酸化，达到与 YT-Org 中相似的程度。与 YT-Org 相比，YT-CB5 中由磷酸酶 (PP) 1 和 PP2A 抑制剂诱导的 ERK1/2 磷酸化也较低。此外，与 NKG2D 珠结合的抗体有助于针对 K562 细胞的细胞毒性，尽管是针对 2B4 的抗体，但在 YT-CB5 中诱导的 ERK1/2 磷酸化可忽略不计。诱导较高水平的磷酸化。此外，与高表达NKG2D的PB-NK细胞相比，低表达NKG2D的外周血（PB-）NK细胞显示出抗NKG2D抗体介导的ERK1/2磷酸化较低。这些结果表明，由于 NKG2D 表达减少，YT-CB5 中导致 ERK 磷酸化的信号转导事件受到损害。需要进一步的研究来澄清石棉暴露对 NK 细胞的抑制作用是否可能促进吸入石棉的人患肺癌和间皮瘤。
YT-CB5, which had been continuously cultured with chrysotile B (CB) asbestos, showed impaired cytotoxicity with decreased expression of NKG2D and 2B4 NK cell-activating receptors. In the present study, the phosphorylation of extracellular signal-regulated kinase (ERK), which is known to induce degranulation downstream of many NK cell-activating receptors, was examined in YT-CB5 by How cytometry and compared with the control line YT-Org. YT-CB5 exhibited impaired phosphorylation of ERK1/2 induced by the recognition of K562 cells, downstream of a process mediated by Src family kinase and phosphoinositide 3-kinase. YT-CB5 also exhibited impaired phosphorylation of ERK1/2 following incubation with K562 cells in the presence of anti-2B4 antibodies, where co-stimulation by 2134 augmented the phosphorylation of ERK1/2 in YT-CB5 to a similar degree as in YT-Org. The phosphorylation of ERK1/2 induced by an inhibitor against phosphatase (PP) 1 and PP2A was also lower in YT-CB5 compared with YT-Org. Moreover, bead-bound antibodies to NKG2D which contribute to cytotoxicity against K562 cells, induced negligible phosphorylation of ERK1/2 in YT-CB5, although antibodies to 2B4. induced a comparatively greater level of phosphorylation. Additionally, peripheral blood (PB-) NK cells with low expression of NKG2D showed lower phosphorylation of ERK1/2 mediated by anti-NKG2D antibodies compared with PB-NK cells with high expression of NKG2D. These results indicate that signal transduction events leading to the phosphorylation of ERK is impaired in YT-CB5 due to decreased expression of NKG2D. Further studies are required to clarify whether this suppressive effect of asbestos exposure on NK cells might promote lung cancer and mesothelioma in people who have inhaled asbestos.