The National Natural Science Foundation of China (General Program, Key Program, Major Research Plan)
目的：探讨神经细胞粘附分子L1样蛋白（cell adhesion molecule L1-like protein, CHL1）在支气管哮喘中表达及潜在机制。方法：收集55名哮喘患者及同期18名健康对照的临床资料及血清标本，酶联免疫吸附法检测血清CHL1水平，分析其与肺功能指标、血清总免疫球蛋白E（immunoglobulin E, IgE）相关性。构建卵清蛋白（ovalbumin, OVA）诱导的慢性过敏性哮喘小鼠模型，免疫组化观察小鼠肺组织CHL1表达定位及分布。采用不同细胞因子刺激人支气管上皮细胞系（16HBE），分别用实时定量PCR法和蛋白质免疫印迹法检测细胞CHL1 mRNA和蛋白表达情况。结果：与对照组（4.174±2.122 ng/ml）相比，哮喘患者血清CHL1水平明显增高（7.497±3.274 ng/ml, p<0.0001）, 与血清总IgE水平成正相关（r=0.2871, p=0.0478）。CHL1主要表达于小鼠肺组织支气管上皮细胞，哮喘小鼠表达量较对照组升高。TGF-β可上调支气管上皮细胞CHL1 mRNA及蛋白表达水平。结论：哮喘中支气管上皮细胞CHL1表达增加，该过程可能与TGF-β相关信号通路有关。
Objective: To study the expression and potential mechanism of cell adhesion molecule L1-like protein (CHL1) in bronchial asthma. Methods: Collect the clinical data and serum samples of 55 asthma patients and 18 healthy controls, use enzyme-linked immunosorbent assay to detect the expression of serum CHL1, then analyze the correlation of CHL1 with pulmonary function related-index, as well as serum total Immunoglobulin E (IgE). A mouse model of ovalbumin (OVA)-induced chronic allergic asthma was constructed, using immunohistochemistry to observe the localization and distribution pattern of CHL1 in lung tissue. Real-time quantitative PCR and western blotting were used to detect the expression of CHL1 after stimulated by different cytokines in human bronchial epithelial cell line 16HBE. Results: The level of serum CHL1 in the asthma group was higher than in the healthy control group [ (7.497±3.274) ng/ml vs. (4.174±2.122) ng/ml, p<0.0001], and is positively correlated with the level of serum total IgE (r=0.2871, p=0.0478). CHL1 is mainly expressed in bronchial epithelial cells in mouse lung tissue, the expression level of asthma mice was higher than that of the control group. After stimulation of exogenous TGF-β at different times, the mRNA and protein levels of CHL1 were up-regulated. Conclusion: The expression of CHL1 is elevated in asthma, and This process may be related to TGF- β related signal pathways.