摘要
目的动态观测MCMV感染对小鼠心肌组织TH1/TH2类细胞因子及其特异性转录因子T-bet／GATA-3表达的影响。方法建立小鼠巨细胞病毒感染心肌炎模型。观察小鼠血清cTnI浓度变化,心肌组织病理损害和心肌组织细胞因子IFN-γ、IL-4表达水平以及脾组织中转录因子T-bet、GA- TA-3表达强度。结果心肌组织病理积分和血清cTnI浓度在MCMV感染后第3天增高,第7天达高峰,第14天仍维持较高水平;IFN-γ在MCMV感染第3天时表达迅速增高达到峰值,随后下降,第14天基本下落至正常水平;IL-4在MCMV感染第5天表达迅速增高达到峰值,随后下降,在第14天又升高;MCMV感染第3天转录因子T-bet蛋白表达达峰值,随后逐渐降低,到第14天时降低更为显著。转录因子GATA-3在MCMV感染第7天时表达明显增强,第14天时增强更为显著。结论MCMV感染通过上调GATA-3转录因子和IL-4表达,下调T-bet转录因子和IFN-γ表达,导致TH1／TH2平衡失调,表现为TH2细胞优势应答状态,使心肌损害加重。这可能是CMV感染致宿主特异性细胞免疫功能降低并造成组织损伤的机制之一。
Objective To investigate the effects of murine cytomegalovirus infection on the expression of TH1/TH2 type cytokines and specific transcription factor T-bet/GATA-3 inducing their differentiation. Methods A BALB/c mice model system of MCMV infection was established. Forty BALB/c mice were randomly divided into MCMV-infected group （n = 20） and blank controls group （n = 20）. All experimental mice were sacrificed at 3, 5, 7, 14 days （n = 5 at each time point） after MCMV infection （p. i. ）. Hearts and spleens were removed under aseptic conditions. One part of each heart was processed with Bouin＇s fixative for histological examination. The other part for testing the expression levels of each heart was immediately forzen in liquid nitrogen and then stored at -80℃ untiU IFN-γ and IL-4 were measured by ELISA. Transcription factor T-bet and GATA-3 of spleen tissue were determined by Western blot analysis. Results Levels of IFN-γ significanfly rose on day 3 p. i., and then dropped to levels similar to those in uninfected mice on day 14 p. i.. Levels of IL-4 significanfly increased on day 14 p. i.. Correspondingly, transcription factor T-bet significantly decreased on day 7 and day 14 p. i., and transcription factor GATA-3 significantly increased on day 7 and day 14 p. i.. Meanwhile, a mixed cellular infiltrate composed of polymorphonuclear neutrophils and mononuclear lymphocytes was observed on days 3, which reached a peak on day 7 p. i.. Seurm cTnl levels were elevated on day 3 p. i., reaching a peak at day 7 p. i.. Conclusion MCMV infection markedly down-modulated the expression of IFN-γ and T-bet, and significantly up-regulated the expression of IL-4 and GATA-3, indicating CMV infection led to the disequilibrium of TH1/TH2 cells＇ differentiation and their cytokines＇ expression, which is likely to suppress the functions of cellular immunity in the infected host and to be one of the reasons of CMV escaping the attack of body＇s specific cellular immunity so that causing persistent or latent infections and even leading to diseases under the certain conditions.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2006年第9期827-830,共4页
Chinese Journal of Microbiology and Immunology
基金
浙江省中医药科技计划项目(2006Y031)
关键词
巨细胞病毒
转录因子
细胞因子
Cytomegalovirus
Transcription factor
Cytokine
作者简介
通讯作者：徐翼，Email：xuyi70@163．com，电话：0571-87061007
