Espinoza-Delgado I, Bosco M C, Musso T, Mood K, Ruscetti F W, Longo D L, Varesio L
Medicine Branch, National Cancer Institute, Bethesda, MD.
Blood. 1994 Jun 1;83(11):3332-8.
We have previously reported that transforming growth factor-beta 1 (TGF-beta 1) inhibits interleukin-6 (IL-6) induction by IL-2 and IL-1 in fresh human monocytes. We investigated the effects of TGF-beta 1 on the expression of tumoricidal activity induced by IL-2 or interferon-gamma (IFN-gamma) in human monocytes. We showed that TGF-beta 1 specifically inhibited, in a dose-dependent manner, IL-2-induced but not IFN-gamma-induced monocyte tumoricidal activity. The inhibitory effects of TGF-beta 1 on IL-2-activated monocytes were not caused by down-modulation of the IL-2 receptor beta (IL-2R beta) because the treatment of monocytes with IL-2 and TGF-beta 1 increased IL-2R beta mRNA expression. However, we found that TGF-beta 1 down-modulated IL-2-induced IL-2R gamma mRNA, which may be responsible for the TGF-beta 1 inhibition of monocyte activation by IL-2. The resistance of the IFN-gamma-induced activation to the inhibitory effects of TGF-beta 1 could be caused by the ability of IFN-gamma to decrease TGF-beta 1 receptor expression, as shown by cross-linking experiments. Overall, these results showed that TGF-beta 1 is a powerful inhibitor of IL-2- but not of IFN-gamma-induced activation of monocytes to a cytotoxic stage. This differential effect may be attributed to modulation of cytokine receptor expression.
我们之前曾报道，转化生长因子-β1（TGF-β1）在新鲜人单核细胞中可抑制白细胞介素-2（IL-2）和白细胞介素-1（IL-1）诱导的白细胞介素-6（IL-6）。我们研究了TGF-β1对人单核细胞中由IL-2或干扰素-γ（IFN-γ）诱导的杀肿瘤活性表达的影响。我们发现，TGF-β1以剂量依赖的方式特异性抑制IL-2诱导的而非IFN-γ诱导的单核细胞杀肿瘤活性。TGF-β1对IL-2激活的单核细胞的抑制作用并非由IL-2受体β（IL-2Rβ）的下调所致，因为用IL-2和TGF-β1处理单核细胞会增加IL-2Rβ mRNA的表达。然而，我们发现TGF-β1下调了IL-2诱导的IL-2Rγ mRNA，这可能是TGF-β1抑制IL-2激活单核细胞的原因。如交联实验所示，IFN-γ诱导的激活对TGF-β1抑制作用的抗性可能是由于IFN-γ降低TGF-β1受体表达的能力所致。总体而言，这些结果表明，TGF-β1是IL-2诱导的而非IFN-γ诱导的单核细胞激活至细胞毒性阶段的强大抑制剂。这种差异效应可能归因于细胞因子受体表达的调节。
