吸入糖皮质激素对哮喘患者诱导痰炎性细胞蛋白激酶Cα表达及白细胞介素-5的影响

目的　观察哮喘患者气道炎性细胞中蛋白激酶C(PKCα)的表达和白细胞介素 (IL) 5的水平 ,及吸入糖皮质激素 (以下简称激素 )对其的影响。方法　 2 9例哮喘患者分为激素治疗 2周组 ( 14例 )和激素治疗 4周组 ( 15例 ) ,治疗前后行诱导痰和肺功能检查。免疫组化 (SP法 )测PKCα在诱导痰炎性细胞中的表达 ,ELISA测诱导痰上清中IL 5的含量。结果　哮喘患者治疗前诱导痰中嗜酸性粒细胞 (EOS)与淋巴细胞相对计数、炎性细胞中PKCα阳性表达率与IL 5含量均高于健康对照组 (P <0 0 1) ,治疗后均明显下降 (P <0 0 1) ,但仍高于健康对照组 (P <0 0 1) ,激素治疗 2周组与激素治疗 4周组间无明显差异 (P >0 0 5 )。第 1秒钟用力呼气容积 (FEV1)占预计值的百分比与炎性细胞中PKCα的阳性表达率、IL 5浓度、EOS相对计数呈负相关 (r =- 0 4 2 3,P <0 0 5 ;r =- 0 6 6 4 ,P <0 0 1;r =-0 5 78,P <0 0 1) ;IL 5浓度与炎性细胞中PKCα的阳性表达率、EOS相对计数呈正相关 (r =0 6 2 3,P<0 0 1;r=0 75 8,P <0 0 1)。结论　PKCα信号途径可能为哮喘气道炎症发生的重要机制之一 ;吸入激素可明显降低气道IL 5的含量和炎性细胞PKCα阳性表达率 ,但短期内不能使气道炎症完全恢复正常

The effect of inhaled glucocorticosteroid on protein kinase C alpha expression and interleukin-5 production in induced sputum inflammatory cells of asthma patients

OBJECTIVE: To investigate the expression of protein kinase C alpha (PKC alpha) in inflammatory cells and the level of interleukin-5 (IL-5) in induced sputum in asthma patients and the effect of inhaled glucocorticosteroid on them. METHODS: 29 asthma patients were classified into 2 groups; 14 patients were treated with fluticasone propionate for 2 weeks and the others were treated with fluticasone propionate for 4 weeks. Induced sputum with inhaled hypertonic saline (4% - 5%) was collected. 13 healthy volunteers were included as controls. Lung ventilatory function and forced expiratory volume in one second (FEV(1)) were measured in all patients. The expression of PKC alpha in the inflammatory cells was detected using immunocytochemistry and the positive percentage in different cells was counted. IL-5 in sputum supernatants was detected using enzyme-linked immunosorbent assay. RESULTS: The percentage of eosinophils (11.1 +/- 4.3)%, lymphocytes (4.3 +/- 2.6)%, PKC alpha positive cells (79.0 +/- 9.6)% and the concentration of IL-5 (64.9 +/- 46.0) ng/L in asthmatics were higher than the percentage of eosinophils (0.7 +/- 0.5)%, lymphocytes (1.1 +/- 0.5)%, PKC alpha positive cells (10.5 +/- 2.3)% and the concentration of IL-5 (14.3 +/- 8.4) ng/L in the controls (P < 0.01). The percentage of PKC alpha positive cells and the concentration of IL-5 in the two groups of asthma were lower than that before fluticasone propionate treatment (P < 0.05), and the forced expiratory volume in first second was correlated to them (respectively, r = -0.423, P < 0.05; n = 29, r = -0.664, P < 0.01). The concentration of IL-5 was correlated to the percentage of PKC alpha positive cells (n = 29, r = 0.623, P < 0.01). CONCLUSIONS: PKC alpha in the inflammatory cells and IL-5 may play an important part in airway inflammation, and the signal transduction of the PKC alpha may be one of the mechanisms of the airway inflammation in asthma. Glucocorticosteroid could suppress the expression of PKC alpha in airway inflammatory cells and then decrease the production of IL-5 in asthmatic airways.