糖皮质激素敏感型、依赖型和抵抗型哮喘患者外周血单个核细胞中糖皮质激素受体和热休克蛋白 90mRNA表达的研究(英文)

Glucocorticoid receptor and heat shock protein 90 in peripheral blood mononuclear cells from asthmatics

目的 探讨糖皮质激素受体 (GR)和热休克蛋白 90 (HSP90 )mRNA在糖皮质激素敏感型 (SS)、依赖型 (SD)和抵抗型 (SR)哮喘中的表达及其在SR哮喘发病中的作用。方法 采用反转录 聚合酶链 (RT PCR)的方法分别测定正常人 (10例 )、SS哮喘 (10例 )、SD哮喘 (5例 )和SR哮喘(6例 )的外周血单个核细胞 (PBMC)中GRmRNA和HSP90mRNA的表达 ,并在体外用IL 2、IL 4分别、联合刺激上述细胞观察其受刺激后GRmRNA和HSP90mRNA表达的改变情况。结果 SR哮喘的GR和HSP90mRNA表达水平最高 (分别为 0 730± 0 171和 1 12 2± 0 165 ) ,SS哮喘次之 (分别为0 35 9± 0 35 0和 0 885± 0 2 5 0 ) ,SD哮喘最低 (分别为 0 0 17± 0 0 0 8和 0 0 78± 0 0 39)。正常人有一定表达 (分别为 0 0 5 2± 0 0 13和 0 362± 0 10 1)。GR和HSP90mRNA的表达各组间相比P <0 0 5。正常人、SS、SD和SR哮喘HSP90 /GR的比值分别为 7 15± 1 84、8 39± 7 95、5 5 1± 3 30、1 5 7± 0 18,SR哮喘HSP90 /GR比值明显低于前三组 (P <0 0 5 )。IL 2和IL 4单独刺激对SS、SD和SR哮喘的GR、HSP90mRNA表达无明显影响 ,二者联合刺激可使SS、SD和SR哮喘GRmRNA表达以及SS、SD哮喘HSP90mRNA表达增强 ,但不能使SR哮喘HSP90mRNA表达增强。结?

Objective To investigate the expression of glucocerticoid receptor (GR) and heat shock protein 90(HSP90) mRNA in peripheral blood mononuclear cells (PBMCs) from steroid-sensitive (SS), steroiddependent (SD) and steroid-resistant (SR) asthmatics patients, and to evaluate the role of GR and HSP90in the pathogenesis of SR.Methods Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expressions of GR and HSP90 mRNA in PBMC stimulated with IL-2 and/or IL-4 from 10 normal volunteers,10 SS, 5 SD and 6 SR patients.Results The expressions of GR and HSP90 mRNA were the highest in PBMC from SR patients (0.730±0.171 and 1.122±0.165, respectively) compared with the normals (P＜0.05). The second was from SS patients (0.359±0.350 and 0.885±0.250, respectively). The lowest was from the SD patients (0.017±0.008 and 0.078 ± 0.039, respectively). The ratio of HSP90/GR in SR was significantly lower than that in the others, and it suggested that the expression of HSP90 mRNA was not sufficient in this group of patients. When PBMC from SS, SD and SR was incubated with IL-2 or IL-4 alone, no changes in GR and HSP90 mRNA expression were observed. While incubated with combination of IL-2 and IL-4, a significantly higher expression of GR mRNA was observed in all asthmatics, and a significantly higher expression of HSP90 mRNA was observed only in SS and SD patients.Conclusion The lowering of HSP90/GR ratio may be one of the causes of SR. IL-2 and IL-4 may play roles in the imbalance of HSP90/GR.