Department of Immunobiology, Okayama University Graduated School of Medicine, Dentistry, and Pharmaceutical Sciences.
Biol Pharm Bull. 2014;37(1):81-6. doi: 10.1248/bpb.b13-00616.
Mast cells are involved in various immunological responses, although it remains unknown how their terminal differentiation is regulated. We previously established a culture model that mimics the process of mast cell maturation in the cutaneous tissue and found that growth factor independent 1 (Gfi1) was up-regulated whereas its paralogue Gfi1b down-regulated. Here we investigated the roles of Gfi1 and Gfi1b in the process of mast cell maturation using a murine mast cell line, MC9. Gfi1 and Gfi1b cDNAs were stably expressed in MC9 cells using the recombinant lentivirus. Histamine synthesis was significantly induced by stem cell factor (SCF) alone, whereas tryptase expression was significantly augmented in the presence of both SCF and Swiss 3T3 cells. Since exogenously expressed Gfi1 and Gfi1b might affect their expression levels in MC9 cells, we investigated the relationship between the expression profiles of Gfi1/Gfi1b proteins and maturation indices, such as histamine synthesis and tryptase expression. The comparison suggested that histamine synthesis during the co-culture period was positively regulated by Gfi1b while augmented expression of tryptase was abolished by one-sided expression of Gfi1/Gfi1b. Our findings indicated the involvement of Gfi1 and Gfi1b in the process of murine mast cell maturation.
肥大细胞参与各种免疫反应，但其终末分化的调控机制尚不清楚。我们之前建立了一个细胞培养模型，模拟皮肤组织中肥大细胞的成熟过程，发现生长因子非依赖性 1（Gfi1）上调，而其同源物 Gfi1b 下调。在这里，我们使用小鼠肥大细胞瘤系 MC9 研究了 Gfi1 和 Gfi1b 在肥大细胞成熟过程中的作用。使用重组慢病毒将 Gfi1 和 Gfi1b cDNA 稳定表达在 MC9 细胞中。干细胞因子（SCF）单独显著诱导组氨酸合成，而在 SCF 和瑞士 3T3 细胞存在的情况下，胰蛋白酶表达显著增强。由于外源性表达的 Gfi1 和 Gfi1b 可能影响 MC9 细胞中的表达水平，因此我们研究了 Gfi1/Gfi1b 蛋白的表达谱与肥大细胞成熟指标（如组氨酸合成和胰蛋白酶表达）之间的关系。比较表明，共培养期间的组氨酸合成受 Gfi1b 的正调控，而胰蛋白酶表达的增强则被 Gfi1/Gfi1b 的单方面表达所抑制。我们的研究结果表明 Gfi1 和 Gfi1b 参与了小鼠肥大细胞的成熟过程。
