Miller B A, Olivieri N, Hope S M, Faller D V, Perrine S P
Division of Pediatric Hematology/Oncology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
J Interferon Res. 1990 Aug;10(4):357-66. doi: 10.1089/jir.1990.10.357.
Interferon-gamma (IFN-gamma) has been shown to influence globin gene expression in cord blood and normal adult progenitor-derived erythroblasts. To explore the influence of IFN-gamma on fetal hemoglobin (HbF) synthesis in the hemoglobinopathies, erythroid progenitors (BFU-E, burst forming unit-erythroid) from patients with sickle cell anemia (SCA) and thalassemia were co-cultured with or without IFN-gamma. Hemoglobin content in progenitor-derived erythroblasts was assessed by radioligand assay (RIA). Co-culture of erythroid progenitors from 12 SCA patients with 200-400 U/ml of IFN-gamma resulted in a significant decrease in picograms of HbF and percent HbF per BFU-E-derived erythroblast. The mean decrease (+/- SEM) of picograms of HbF per cell and percent of HbF was by 42 +/- 9% and 35 +/- 8% of control cultures, respectively. Co-culture of erythroid progenitors from 10 patients with thalassemia major or thalassemia variant (HPFH/thalassemia, sickle/beta 0-thalassemia) with 200 U/ml IFN-gamma also resulted in a significant decrease in picograms and percent of HbF per BFU-E-derived erythroblast. IFN-gamma treatment also inhibited the enhancement in gamma-globin synthesis induced in culture by butyric acid. Erythroid progenitors from 2 patients with SCA, 1 patient with sickle/beta 0-thalassemia, and 1 patient with HbE/beta 0-thalassemia were co-cultured with IFN-gamma, L-alpha-amino-n-butyric acid, or both. HbF content (expressed as picograms HbF/cell) was decreased in samples co-cultured with IFN, increased in cultures with L-alpha-amino-n-butyric acid, but remained at control values in cultures treated with IFN plus L-alpha-amino-n-butyric acid. These data demonstrate that IFN-gamma is an environmental factor that influences gamma-globin gene expression in the beta hemoglobinopathies in vitro.
γ干扰素（IFN-γ）已被证明可影响脐血和正常成人祖细胞来源的成红细胞中的珠蛋白基因表达。为了探究IFN-γ对血红蛋白病中胎儿血红蛋白（HbF）合成的影响，将镰状细胞贫血（SCA）和地中海贫血患者的红系祖细胞（BFU-E，爆式红系集落形成单位）与IFN-γ进行共培养或不进行共培养。通过放射配体分析（RIA）评估祖细胞来源的成红细胞中的血红蛋白含量。12例SCA患者的红系祖细胞与200 - 400 U/ml的IFN-γ共培养，导致每个BFU-E来源的成红细胞中HbF的皮克数和HbF百分比显著降低。每个细胞中HbF皮克数的平均降低幅度（±SEM）和HbF百分比分别为对照培养物的42±9%和35±8%。10例重型地中海贫血或地中海贫血变异型（HPFH/地中海贫血、镰状/β0-地中海贫血）患者的红系祖细胞与200 U/ml IFN-γ共培养，也导致每个BFU-E来源的成红细胞中HbF的皮克数和百分比显著降低。IFN-γ处理还抑制了丁酸在培养物中诱导的γ珠蛋白合成增强。2例SCA患者、1例镰状/β0-地中海贫血患者和1例HbE/β0-地中海贫血患者的红系祖细胞与IFN-γ、L-α-氨基-n-丁酸或两者进行共培养。与IFN共培养的样本中HbF含量（以皮克HbF/细胞表示）降低，与L-α-氨基-n-丁酸共培养的培养物中HbF含量增加，但在IFN加L-α-氨基-n-丁酸处理的培养物中保持在对照值。这些数据表明，IFN-γ是一种在体外影响β血红蛋白病中γ珠蛋白基因表达的环境因素。
