酪氨酸蛋白激酶p59fyn在白细胞介素-7诱导皮肤T细胞淋巴瘤信号传导中的作用(英文)

Involvement of the tyrosine kinase p59fyn in induced signal transduction by interleukin 7 in CTCL *

目的：探讨ＩＬ７对纯化瘤性Ｔ细胞群生长信号的刺激作用。白细胞介素（ＩＬ）７能刺激一些良性和恶性淋巴细胞群，包括来自皮肤Ｔ细胞淋巴瘤（ＣＴＣＬ）病人的肿瘤细胞。由于角化细胞产生ＩＬ７，因而ＩＬ７可能在ＣＴＣＬ和其他炎性皮肤病的生物学上起作用。方法：细胞从ＣＴＣＬ患者外周血中分离，体外ＩＬ７处理１～１０ｍｉｎ，ＤＮＡ合成法检测细胞的增殖。应用免疫沉淀和Ｗｅｓｔｅｒｎ印迹技术，研究酪氨酸激酶类对ＩＬ７的信号应答。结果：与正常Ｔ细胞不同的是，在无丝裂原下用ＩＬ７体外培养的ＣＴＣＬ细胞增殖。ＩＬ７孵育之后细胞内不同底物快速发生酪氨酸磷酸化。ｇｅｎｉｓｔｅｉｎ能抑制其细胞增殖和酪氨酸磷酸化。Ｓｒｃ家族蛋白之一酪氨酸激酶ｐ５９ｆｙｎ，在ＩＬ７处理１ｍｉｎ内发生酪氨酸磷酸化，而作为酪氨酸磷酸化可能候选的ＰＩ３激酶的ｐ８５亚基并未发生。结论：提示ＩＬ７诱导酪氨酸蛋白激酶ｐ５９ｆｙｎ是其介导信号传导途径的早期事件，且在ＣＴＣＬ的病理生理学中起重要作用。

Aim:The purpose of this study was to investigate the growth signal triggered by interleukin 7 (IL 7) in a purified population of neoplastic T cells.IL 7 stimulates proliferation of several benign and malignant lymphocyte populations,including tumor cells from patients with cutaneous T cell lymphoma (CTCL). Since IL 7 is produced by keratinocytes,this cytokine may play a role in the biology of CTCL and other inflammatory skin disease.Methods: Cells were isolated from peripheral blood of CTCL patients.After the cells being treated in vitro with IL 7 for 1～10 minutes,their proliferations were determined by DNA sythesis method.We studied tyrosine kinasis in signaling in response to IL 7 usingimmunoprecipitation and Western blot technique.Results: Our fingdings confirmed that CTCL cells,unlike normal T cells,proliferated in vitro when cultured with IL 7 in the absence of mitogen.IL 7 incubation was followed by rapid tyrosine phosphorylation ofdistinct intracellular substrates. Both cell proliferation and tyrosine phosphorylation were inhibited by genistein.The Src family protein tyrosine kinase p59fyn was tyrosine phosphorylated within one minute of IL 7 treatment,but the p85 subunit of PI 3 Kinase,a likely candidate for tyrosine phosphorylation,was not.Conclusion: These results provide information regarding the early events of the IL 7 signal transduction and suggest that this cytokine may play an important role in the pathophysiology of CTCL.