呼吸道合胞病毒感染对小鼠呼吸道上皮CFTR氯离子通道表达的影响
|
摘要
目的:探讨呼吸道合胞病毒(respiratory syncytial virus,RSV)感染小鼠支气管上皮细胞后对囊性纤维化跨膜转运调节体(cystic fibrosis transmembrane conductance regulator,CFTR)氯离子通道表达的影响。方法:44只6～8周雌性BALB/c小鼠随机分为对照组和RSV组,运用qRT-PCR技术检测对照组、RSV组在不同时间点CFTR mRNA表达水平。结果:RSV感染BALB/c小鼠第7天时,RSV组CFTR mRNA表达水平低于对照组(n=11,P<0.05);感染第14天时,RSV组CFTR mRNA表达水平高于对照组(n=11,P<0.05)。结论:当小鼠在感染RSV初期,支气管上皮细胞CFTR氯离子通道基因表达水平下调,而随着感染时间的延长,支气管上皮细胞CFTR氯离子通道基因表达水平上调。CFTR氯离子通道可能是RSV感染后调控呼吸道上皮黏液分泌的下游靶标,这为药物研发提供了新思路。
Objective: To investigate the expression of CFTR chloride channels after respiratory syncytial virus infection in mouse respiratory epithelium. Methods: Forty-eight female BA LB/c mice aged(6 ～ 8 weeks) were randomly divided into two groups: control and RSV(n=11 each). The expression of CFTR mRNA in control group and RSV group was detected by qRT-PCR. Results: On 7 th day of RSV-infected BA LB/c mice, the expression of CFTR mRNA in RSV group was lower than that in control group(n = 11, P<0.05). On the 14 th day of infection, the expression of CFTR mRNA in RSV group was higher than that in control group(n = 11,P < 0.05). Conclusion: W hen the mice were infected with RSV on the 7 th day, we detected the down-regulation of CFTR chloride channel gene expression in bronchial epithelial cells. With the prolonged infection of RSV in time, and on the 14 th day, the CFTR chloride channel gene expression levels of bronchial epithelial cells were up-regulated. The CFTR chloride channel may be a downstream target for respiratory mucosal mucus secretion after RSV infection, which provides new ideas for drug development.
Objective: To investigate the expression of CFTR chloride channels after respiratory syncytial virus infection in mouse respiratory epithelium. Methods: Forty-eight female BA LB/c mice aged(6 ～ 8 weeks) were randomly divided into two groups: control and RSV(n=11 each). The expression of CFTR mRNA in control group and RSV group was detected by qRT-PCR. Results: On 7 th day of RSV-infected BA LB/c mice, the expression of CFTR mRNA in RSV group was lower than that in control group(n = 11, P<0.05). On the 14 th day of infection, the expression of CFTR mRNA in RSV group was higher than that in control group(n = 11,P < 0.05). Conclusion: W hen the mice were infected with RSV on the 7 th day, we detected the down-regulation of CFTR chloride channel gene expression in bronchial epithelial cells. With the prolonged infection of RSV in time, and on the 14 th day, the CFTR chloride channel gene expression levels of bronchial epithelial cells were up-regulated. The CFTR chloride channel may be a downstream target for respiratory mucosal mucus secretion after RSV infection, which provides new ideas for drug development.
引文
[1]SHI T,MCA LLISTER D A,O'BRIEN K L,et al.Global,regional,and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015:a systematic review and modelling study[J].Lancet,2017,390(10098):946-958.
[2]CHAV EZ-BUENO S,MEJIA S A,JA FRI H S,et al.Respiratory syncytial virus:old challenges and new approaches[J].Pediatr A nn,2005,34(1):62-68.
[3]欧少阳,林广裕,吴扬,等.粤东地区住院小儿急性下呼吸道感染病毒病原学研究[J].中国当代儿科杂志,2009,11(3):203-206.
[4]袁艺,宋国维,杜军保,等.北京地区住院急性呼吸道感染患儿的病毒病原检测分析[J].实用儿科临床杂志,2006,21(6):348-350.
[5]W IDDICOMBE J H,W INE J J.A irway gland structure and function[J].Physiol Rev,2015,95(4):1241-1319.
[6]陈智鸿,白春学.气道黏液高分泌与上皮通道蛋白关系的研究进展[J].国际呼吸杂志,2007,27(11):870-872.
[7]A NA GNOSTOPOULOU P,DA I L,SCHATTERNY J,et al.A llergic airway inflammation induces a prosecretory epithelial ion transport phenotype in mice[J].Eur Respir J,2010,36(6):1436-1447.
[8]W IDDICOMBE J H.Regulation of the depth and composition of airway surface liquid[J].J A nat,2002,201(4):313-318.
[9]ENGELHA RDT J F,YA NKA SKA S J R,Ernst S A,et al.Submucosal glands are the predominant site of CFTR expression in the human bronchus[J].Nat Genet,1992,2(3):240-248.
[10]KREDA S M,MA LL M,MENGOS A,et al.Characterization of wild-type and deltaF508 cystic fibrosis transmembrane regulator in human respiratory epithelia[J].Mol Biol Cell,2005,16(5):2154-2167.
[11]W ILSCHA NSKI M.Novel therapeutic approaches for cystic fibrosis[J].Discov Med,2013,15(81):127-133.
[12]GRA HA M B S,PERKINS M D,W RIGHT P F,et al.Primary respiratory syncytial virus infection in mice[J].J Med Virol,1988,26(2):153-162.
[13]PA RA MORE L C,CIURY LA V,CIESLA G,et al.Economic impact of respiratory syncytial virus-related illness in the US:an analysis of national databases[J].Pharmacoeconomics,2004,22(5):275-284.
[14]HAY NES A K,MA NA NGA N A P,IWA NE M K,et al.Respiratory syncytial virus circulation in seven countries with Global Disease Detection Regional Centers[J].J Infect Dis,2013,208(Suppl 3):S246-S254.
[15]HA LL C B.The burgeoning burden of respiratory syncytial virus among children[J].Infect Disord Drug Targets,2012,12(2):92-97.
[16]JORQUERA P A,A NDERSON L,TRIPP R A.Understanding respiratory syncytial virus(RSV)vaccine development and aspects of disease pathogenesis[J].Expert Rev Vaccines,2016,15(2):173-187.
[17]BUKREY EV A,CA MA RGO E,COLLINS P L.Recovery of infectious respiratory syncytial virus expressing an additional,foreign gene[J].J Virol,1996,70(10):6634-6641.
[18]BECKER Y.Respiratory syncytial virus(RSV)evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE,markers of allergy--a review[J].Virus Genes,2006,33(2):235-252.
[19]GA LIETTA L J,PA GESY P,FOLLI C,et al.IL-4 is a potent modulator of ion transport in the human bronchial epithelium in vitro[J].J Immunol,2002,168(2):839-845.
[20]DA NA HAY H,ATHERTON H,JONES G,et al.Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells[J].A m JPhysiol Lung Cell Mol Physiol,2002,282(2):L226-L236.
[2]CHAV EZ-BUENO S,MEJIA S A,JA FRI H S,et al.Respiratory syncytial virus:old challenges and new approaches[J].Pediatr A nn,2005,34(1):62-68.
[3]欧少阳,林广裕,吴扬,等.粤东地区住院小儿急性下呼吸道感染病毒病原学研究[J].中国当代儿科杂志,2009,11(3):203-206.
[4]袁艺,宋国维,杜军保,等.北京地区住院急性呼吸道感染患儿的病毒病原检测分析[J].实用儿科临床杂志,2006,21(6):348-350.
[5]W IDDICOMBE J H,W INE J J.A irway gland structure and function[J].Physiol Rev,2015,95(4):1241-1319.
[6]陈智鸿,白春学.气道黏液高分泌与上皮通道蛋白关系的研究进展[J].国际呼吸杂志,2007,27(11):870-872.
[7]A NA GNOSTOPOULOU P,DA I L,SCHATTERNY J,et al.A llergic airway inflammation induces a prosecretory epithelial ion transport phenotype in mice[J].Eur Respir J,2010,36(6):1436-1447.
[8]W IDDICOMBE J H.Regulation of the depth and composition of airway surface liquid[J].J A nat,2002,201(4):313-318.
[9]ENGELHA RDT J F,YA NKA SKA S J R,Ernst S A,et al.Submucosal glands are the predominant site of CFTR expression in the human bronchus[J].Nat Genet,1992,2(3):240-248.
[10]KREDA S M,MA LL M,MENGOS A,et al.Characterization of wild-type and deltaF508 cystic fibrosis transmembrane regulator in human respiratory epithelia[J].Mol Biol Cell,2005,16(5):2154-2167.
[11]W ILSCHA NSKI M.Novel therapeutic approaches for cystic fibrosis[J].Discov Med,2013,15(81):127-133.
[12]GRA HA M B S,PERKINS M D,W RIGHT P F,et al.Primary respiratory syncytial virus infection in mice[J].J Med Virol,1988,26(2):153-162.
[13]PA RA MORE L C,CIURY LA V,CIESLA G,et al.Economic impact of respiratory syncytial virus-related illness in the US:an analysis of national databases[J].Pharmacoeconomics,2004,22(5):275-284.
[14]HAY NES A K,MA NA NGA N A P,IWA NE M K,et al.Respiratory syncytial virus circulation in seven countries with Global Disease Detection Regional Centers[J].J Infect Dis,2013,208(Suppl 3):S246-S254.
[15]HA LL C B.The burgeoning burden of respiratory syncytial virus among children[J].Infect Disord Drug Targets,2012,12(2):92-97.
[16]JORQUERA P A,A NDERSON L,TRIPP R A.Understanding respiratory syncytial virus(RSV)vaccine development and aspects of disease pathogenesis[J].Expert Rev Vaccines,2016,15(2):173-187.
[17]BUKREY EV A,CA MA RGO E,COLLINS P L.Recovery of infectious respiratory syncytial virus expressing an additional,foreign gene[J].J Virol,1996,70(10):6634-6641.
[18]BECKER Y.Respiratory syncytial virus(RSV)evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE,markers of allergy--a review[J].Virus Genes,2006,33(2):235-252.
[19]GA LIETTA L J,PA GESY P,FOLLI C,et al.IL-4 is a potent modulator of ion transport in the human bronchial epithelium in vitro[J].J Immunol,2002,168(2):839-845.
[20]DA NA HAY H,ATHERTON H,JONES G,et al.Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells[J].A m JPhysiol Lung Cell Mol Physiol,2002,282(2):L226-L236.