Giovannetti A, Aiuti A, Pizzoli P M, Pierdominici M, Agostini E, Oliva A, Dianzani F, Aiuti F, Pandolfi F
Department of Clinical Immunology and Allergy, La Sapienza University of Rome, Italy.
Clin Exp Immunol. 1995 Apr;100(1):157-63. doi: 10.1111/j.1365-2249.1995.tb03618.x.
The molecular mechanisms regulating IFN-gamma production have yet to be well characterized. We describe here how treatment of activated cultures of peripheral blood mononuclear cells (PBMC) with the phosphotyrosine phosphatases (PTP) inhibitor sodium ortho vanadate results in greatly enhanced IFN-gamma production. Conversely, cellular proliferation of the same cultures is profoundly inhibited by treatment with vanadate, while the expression of IL-2R and DR molecules on activated lymphocytes remains substantially unmodified. Increased IFN-gamma production, but not inhibition of cellular proliferation, was also observed in mitogen-activated vanadate-treated Jurkat cells. On the other hand, IFN-gamma production induced in cultures of PBMC treated or not with vanadate, was strongly inhibited by incubation with the protein tyrosine kinase (PTK) inhibitor herbimycin A. As a result of the inhibited phosphatase activity, substrates for PTK become hyperphosphorylated on tyrosine residues, as shown by Western blot analysis of cell lysates from cultures of PBMC treated with vanadate. We suggest that the tyrosine phosphorylation pathway plays a role in regulating IFN-gamma production.
调节γ干扰素产生的分子机制尚未得到充分阐明。我们在此描述了用磷酸酪氨酸磷酸酶（PTP）抑制剂原钒酸钠处理外周血单个核细胞（PBMC）活化培养物如何导致γ干扰素产生大幅增强。相反，用钒酸盐处理会显著抑制相同培养物的细胞增殖，而活化淋巴细胞上IL-2R和DR分子的表达基本未改变。在用丝裂原激活的钒酸盐处理的Jurkat细胞中也观察到γ干扰素产生增加，但细胞增殖未受抑制。另一方面，用蛋白酪氨酸激酶（PTK）抑制剂赫曲霉素A孵育，强烈抑制了用或未用钒酸盐处理的PBMC培养物中诱导的γ干扰素产生。由于磷酸酶活性受到抑制，PTK的底物在酪氨酸残基上过度磷酸化，这在用钒酸盐处理的PBMC培养物的细胞裂解物进行的蛋白质印迹分析中得到了证实。我们认为酪氨酸磷酸化途径在调节γ干扰素产生中起作用。
