Expression of interleukin-9 in nasal natural killer/T-cell lymphoma cell lines and patients

Expression of interleukin-9 in nasal natural killer/T-cell lymphoma cell lines and patients
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DOI:
10.1158/1078-0432.ccr-05-1426
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发表时间:
2005-12-01
影响因子:
11.5
通讯作者:
Harabuchi, Y
Harabuchi, Y
中科院分区:
医学1区
文献类型:
--
作者:
Nagato, T;Kobayashi, H;Harabuchi, Y

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目的:鼻自然杀伤(NK)/T细胞淋巴瘤与EB病毒相关,具有独特的临床和组织学特征。然而,人们对其遗传特征知之甚少。本研究通过对鼻NK/T细胞淋巴瘤细胞株SNK-6和SNT-8基因表达谱的检测,发现白细胞介素(IL)-9在这两种细胞株中特异性表达。用逆转录-PCR、ELISA和流式细胞术检测IL-9及其受体的表达。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定评估细胞生长。结果:在cDNA芯片中,SNK-6和SNT-8细胞中IL-9 mRNA的表达明显高于非鼻NK细胞淋巴瘤的NK-92细胞和健康人外周血单个核细胞。此外,IL-9在SNK-6和SNT-8细胞中特异性表达,但在其他NK细胞、NK样T细胞和T细胞淋巴瘤/白血病细胞系中不表达。SNK-6和SNT-8细胞表面也表达IL-9受体。IL-9中和抗体抑制了这两种细胞系的生长,而重组人IL-9增强了它们的生长。结论:IL-9在鼻NK/T细胞淋巴瘤中可能通过自分泌机制发挥重要作用。
Purpose: Nasal natural killer (NK)/T-cell lymphoma is associated with EBV and has distinct clinical and histologic features. However, little is known about its genetic features. In this study, we examined the genes expressed by SNK-6 and SNT-8 cells, which were established from nasal NK/T-cell lymphomas, and found that interleukin (IL)-9 was specifically expressed in these two cell lines.Experimental Design: cDNA array was used to examine the genes expressed by SNK-6 and SNT-8 cells. Expression of IL-9 and IL-9 receptor was investigated by reverse transcription- PCR, ELISA, and flow cytometry. Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Immunohistologic staining and ELISA were used to examine IL-9 expression in biopsies and sera from patients, respectively.Results: In cDNA array, expression of IL-9 mRNA was much higher in SNK-6 and SNT-8 cells than in NK-92 cells from non-nasal NK-cell lymphoma and peripheral blood mononuclear cells from healthy volunteers. Furthermore, IL-9 was specifically expressed by SNK-6 and SNT-8 cells but not by other NK-cell, NK-like T-cell, and T-cell lymphoma/leukemia cell lines. IL-9 receptor was also expressed on the surfaces of SNK-6 and SNT-8 cells. An IL-9 -neutralizing antibody inhibited the growth of these two cell lines, whereas recombinant human IL-9 enhanced their growth. Most significantly, IL-9 was present in biopsies and sera from patients with this lymphoma,Conclusions: These results suggest that IL-9 plays an important role in nasal NK/T-cell lymphoma possibly via an autocrine mechanism.