Zhou Bing, Han De-min, Wang Tong, Wang Xiang-dong, Fan Er-zhong, Liu Zhong-yan
Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Tongren Hospital Affiliated to the Capital University of Medical Sciences, Beijing 100730, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2005 Jun;40(6):444-8.
To investigate whether the local application of IL-12 gene with EBV-plasmid vector to nasal mucosa could prevent allergic inflammation in murine allergic rhinitis model.
Thirty-six BALB/C mice were randomly divided into allergic rhinitis group gene therapy group and control group. In mice with OVA-induced allergic rhinitis, the EBV/lipoplex (a novel cationic lipid combined with EBV-plasmid vector, pGEG. mIL-12) was locally administered into nasal mucosa before OVA challenge. The expression of IL-12 mRNA and protein, the change of eosinophilia and mast cell, and Th2 cytokine production in the nasal mucosa were measured.
The amounts of IL-12 mRNA positive cells and IL-12 positive cells in nasal mucosa of gene therapy group were significantly higher than that of allergic rhinitis group (P < 0.01 and P < 0.05). The amount of eosinophils, mast cells, and the level of IL-5 expression in nasal mucosa in allergic rhinitis group were significantly higher than those in gene therapy group and control group (P < 0.01). The level of total IgE of peripheral blood in allergic rhinitis group was significantly higher than that in gene therapy group and control group (F = 1216.21, P < 0.01).
These findings indicated that IL-12 mRNA and protein were expressed effectively after the local administration of pGEG. mIL-12 in the nasal mucosa. The local application of pGEG. mIL-12 is effective in modulating nasal allergic response and may be a convenient method for future approach to allergic rhinitis.
研究用EBV质粒载体将白细胞介素-12(IL-12)基因局部应用于鼻黏膜是否能预防小鼠变应性鼻炎模型中的变应性炎症。
将36只BALB/C小鼠随机分为变应性鼻炎组、基因治疗组和对照组。在卵清蛋白(OVA)诱导的变应性鼻炎小鼠中,于OVA激发前将EBV/脂质复合物(一种新型阳离子脂质与EBV质粒载体pGEG.mIL-12结合物)局部应用于鼻黏膜。检测鼻黏膜中IL-12 mRNA和蛋白的表达、嗜酸性粒细胞和肥大细胞的变化以及Th2细胞因子的产生。
基因治疗组鼻黏膜中IL-12 mRNA阳性细胞和IL-12阳性细胞数量显著高于变应性鼻炎组(P<0.01和P<0.05)。变应性鼻炎组鼻黏膜中嗜酸性粒细胞、肥大细胞数量及IL-5表达水平显著高于基因治疗组和对照组(P<0.01)。变应性鼻炎组外周血总IgE水平显著高于基因治疗组和对照组(F=1216.21,P<0.01)。
这些结果表明,在鼻黏膜局部应用pGEG.mIL-12后,IL-12 mRNA和蛋白能有效表达。局部应用pGEG.mIL-12可有效调节鼻变应性反应,可能是未来治疗变应性鼻炎的一种便捷方法。