Yale University School of Medicine, New Haven, CT 06520, USA.
Cytokine. 2009 Dec;48(3):177-85. doi: 10.1016/j.cyto.2009.07.002. Epub 2009 Jul 30.
Macrophage migration inhibitory factor (MIF) is an upstream activator of the immune response that counter-regulates the immunosuppressive effects of glucocorticoids. While MIF is released by cells in response to diverse microbial and invasive stimuli, evidence that glucocorticoids in low concentrations also induce MIF secretion suggests an additional regulatory relationship between these mediators. We investigated the expression of MIF from the human CEM T cell line, which exists in two well-characterized, glucocorticoid-sensitive (CEM-C7) and glucocorticoid-resistant (CEM-C1) variant clones. Dexamethasone in low concentrations induced MIF secretion from CEM-C7 but not CEM-C1 T cells by a bell-shaped dose response that was similar to that reported previously for the release of MIF by monocytes/macrophages. Glucocorticoid stimulation of CEM-C7 T cells was accompanied by an MIF transcriptional response, which by promoter analysis was found to involve the GRE and ATF/CRE transcription factor binding sites. These data support a glucocorticoid-mediated MIF secretion response by T cells that may contribute to the regulation of the adaptive immune response.
巨噬细胞移动抑制因子(MIF)是一种免疫反应的上游激活剂,可拮抗糖皮质激素的免疫抑制作用。虽然 MIF 是细胞在受到各种微生物和侵袭性刺激时释放的,但低浓度的糖皮质激素也能诱导 MIF 分泌的证据表明,这些介质之间存在额外的调节关系。我们研究了人类 CEM T 细胞系中 MIF 的表达,该细胞系存在两种特征明确的、糖皮质激素敏感(CEM-C7)和糖皮质激素抵抗(CEM-C1)变体克隆。低浓度的地塞米松通过钟形剂量反应诱导 CEM-C7 而不是 CEM-C1 T 细胞分泌 MIF,该反应与先前报道的单核细胞/巨噬细胞释放 MIF 的反应相似。糖皮质激素刺激 CEM-C7 T 细胞伴随着 MIF 的转录反应,通过启动子分析发现该反应涉及 GRE 和 ATF/CRE 转录因子结合位点。这些数据支持 T 细胞的糖皮质激素介导的 MIF 分泌反应,这可能有助于调节适应性免疫反应。