转化生长因子-β2在小鼠过敏性气道炎症及重塑中的作用与干预潜能  

Roles of transforming growth factor-β2 in allergen-induced airway inflammation and remodeling of mice and its potentials as an intervention target

作　　者：严皎 白红妹[1] 杨旭[1] 孙文佳[1] 龙琼[1] 马雁冰[1] YAN Jiao;BAI Hongmei;YANG Xu;SUN Wenjia;LONG Qiong;MA Yanbing(Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming 650118,Yunnan Province,China)

机构地区：[1]中国医学科学院北京协和医学院医学生物学研究所,云南昆明650118

出　　处：《中国生物制品学杂志》2024年第8期938-944,951,共8页Chinese Journal of Biologicals

基　　金：国家自然科学基金(81773270);云南省应用基础研究计划重点项目(2016FA049)。

摘　　要：目的探讨转化生长因子-β2(transforming growth factor-β2,TGF-β2)在过敏原引起的哮喘气道炎症和重塑中的作用及其靶向干预的治疗潜能。方法以呈现TGF-β2肽表位的乙型肝炎病毒核心抗原(HBcAg)/TGF-β2病毒样颗粒(virus-like particles,VLPs)免疫6只雌性BALB/c小鼠,ELISA法检测小鼠血清中TGF-β2特异的IgG应答,细胞试验检测抗体对TGF-β2活性的中和能力。卵清白蛋白(ovalbumin,OVA)短期刺激诱导急性气道过敏性炎症,细胞试验检测小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中TGF-β活性水平;ELISA法检测小鼠血清中OVA特异的IgE水平;光学显微镜下进行BALF中炎性细胞总数及分型计数,并用ELISA法检测BALF中细胞因子水平。经OVA慢性刺激诱导气道纤维化,肺组织切片Masson’s trichrome检测胶原积累,并用Sircol胶原检测试剂盒进行可溶性胶原含量定量分析。结果VLPs免疫诱导了TGF-β2特异性IgG应答,抗血清可有效中和TGF-β2活性。小鼠急性气道过敏性炎症模型中,VLPs免疫下调了气道活性TGF-β水平,显著促进了血清中OVA特异性IgE产生,对气道以嗜酸性粒细胞为主的炎性细胞浸润显示抑制作用,显著促进了Th2炎性细胞因子在气道中的积累。慢性肺纤维化模型中,VLPs免疫显著下调了肺组织胶原沉积及可溶性胶原水平。结论HBcAg/TGF-β2 VLPs免疫是调控TGF-β2作用的有效手段,TGF-β2在过敏原诱导的炎症应答中总体显示抑制作用,但在纤维化中发挥促进作用。Objective To investigate the roles of transforming growth factor-β2(TGF-β2)in allergen-induced asthmatic airway inflammation and remodeling and its potentials as an intervention target.Methods Six female BALB/c mice were immu-nized with hepatitis B virus core antigen(HBcAg)/TCF-β2 virus-like particles(VLPs)presenting TGF-β2 epitope.The TGF-β2 specific IgG response in serum of mice was detected by ELISA,and the neutralizing activity of antibody against TGF-β2 was detected by cell test.Acute airway allergic inflammation was induced by a short-term stimulation procedure of ovalbumin(OVA),and the activity of TGF-βin bronchoalveolar lavage fluid(BALF)of mice was detected by cell test.ELISA was used to detect the level of OVA-specific IgE in serum of mice.The total number and type of inflammatory cells in BALF were counted under optical microscope,and the levels of cytokines were detected by ELISA.After sustained stimulation of OVA to induce airway fibrosis,the collagen deposition was detected by Masson's trichrome staining in lung tissue sections,and the soluble collagen content was quantitatively analyzed by Sircol collagen assay kit.Results VLPs immunization induced TGF-β2 specific IgG response,and the antiserum effectively neutralized TCF-β2 activity.In the mouse model of acute airway allergic inflammation,VLPs immunization down-regulated the level of active TCF-βin airway,significantly elevated the production of OVA-specific IgE in serum,suppressed the infiltration of airway inflammatory cells mainly containing eosinophils,and significantly promoted the accumulation of Th2 inflammatory cytokines in airway.In chronic pulmonary fibrosis model,VLPs immunization significantly down-regulated collagen deposition and soluble collagen level in lung tissue.Conclusion HBcAg/TGF-β2 VLPs immunization was an effective means to regulate the effect of TCF-β2.TGF-β2 basically showed suppressive effects on airway inflammatory response induced by allergens,while promoted the fibrosis.

关 键 词：转化生长因子-Β2 病毒样颗粒 卵清白蛋白 气道炎症 纤维化 哮喘 

分 类 号：R392.8[医药卫生—免疫学] R364.7[医药卫生—基础医学]