Dubinett S M, Huang M, Dhanani S, Wang J, Beroiza T
Department of Medicine, Jonsson Comprehensive Cancer Center, UCLA School of Medicine.
J Immunol. 1993 Dec 15;151(12):6670-80.
Transforming growth factor-beta (TGF-beta) is a potent inhibitor of immune responses. Macrophage-derived products, including TGF-beta, have been suggested as inhibitors of the antitumor immune response. We hypothesized that IL-7, a cytokine with antitumor properties, may exert its immunoregulatory effects in part through the down-regulation of TGF-beta. To test this hypothesis we analyzed IL-2-stimulated murine macrophage TGF-beta mRNA expression following exposure to IL-7 both in vitro and in vivo. IL-7 down-regulated IL-2-induced TGF-beta expression by macrophages in vitro, as well as after i.p. injections of IL-2 and IL-7 in vivo. The IL-7-mediated inhibition of TGF-beta mRNA expression did not require new protein synthesis and therefore appears to be a direct effect of IL-7. IL-7 had no significant effect on the stability of TGF-beta mRNA. Nuclear run-on assays revealed that the suppression of IL-2-induced TGF-beta gene expression by IL-7 is mediated at the level of transcription. Also, IL-7 decreased TGF-beta secretion as measured by bioassay. We conclude that IL-7 down-regulates TGF-beta and suggest that some of the proliferative and cytolytic activities mediated by cells exposed to IL-7 may be caused by a decrement in macrophage-derived TGF-beta.
转化生长因子-β（TGF-β）是免疫反应的一种强效抑制剂。包括TGF-β在内的巨噬细胞衍生产物已被认为是抗肿瘤免疫反应的抑制剂。我们推测，具有抗肿瘤特性的细胞因子白细胞介素-7（IL-7）可能部分通过下调TGF-β发挥其免疫调节作用。为了验证这一假设，我们在体外和体内分析了暴露于IL-7后白细胞介素-2刺激的小鼠巨噬细胞TGF-β mRNA表达情况。IL-7在体外以及体内腹腔注射IL-2和IL-7后，均可下调巨噬细胞中IL-2诱导的TGF-β表达。IL-7介导的TGF-β mRNA表达抑制不需要新的蛋白质合成，因此似乎是IL-7的直接作用。IL-7对TGF-β mRNA的稳定性没有显著影响。细胞核转录分析表明，IL-7对IL-2诱导的TGF-β基因表达的抑制作用是在转录水平介导的。此外，通过生物测定法检测发现，IL-7可降低TGF-β的分泌。我们得出结论，IL-7可下调TGF-β，并表明暴露于IL-7的细胞介导的一些增殖和细胞溶解活性可能是由巨噬细胞衍生的TGF-β减少所致。
