PDF(Pubmed)
Abstract：
BACKGROUND: Thymic atrophy is characterized by loss of thymocytes, destruction of thymic architecture, and a subsequent decrease in naïve T cells with compromised immunity. Thymic atrophy occurs during aging. Environmental factors including alcohol misuse also induce thymic atrophy. Despite the link between alcohol misuse and thymic atrophy, the underlying mechanism is understudied. We aimed to identify molecules and signaling pathways that underly alcohol-induced thymic atrophy during aging.
METHODS: F344 rats were given 3-day binge-ethanol (4.8 g/kg/day; 52% w/v; i.g.) and the thymus was collected and weighed. Molecular mechanisms underlying ethanol-induced thymic atrophy were investigated by network meta-analysis using the QIAGEN Ingenuity Pathway Analysis (IPA). The molecules associated with ethanol were identified from the QIAGEN Knowledge Base (QKB) and those associated with thymic atrophy were identified from QKB and Mouse Genome Informatics (MGI). Aging-mediated Differential Expression Genes (DEGs) from mouse thymocytes were obtained from the Gene Expression Omnibus (GEO) database (GSE132136). The relationship between the molecules and associated signaling pathways were studied using IPA.
RESULTS: Binge-ethanol decreased thymic weight in F344 rats. Our meta-analysis using IPA identified molecules commonly shared by ethanol and thymic atrophy through which simulation with ethanol increased thymic atrophy. We then obtained aging-mediated DEGs from the atrophied thymocytes. We found that ethanol contributed to thymic atrophy through modulation of the aging-mediated DEGs. Our network meta-analysis suggests that ethanol may augment thymic atrophy through increased expression of cytokines (e.g., IL-6, IL-17A and IL-33) along with their regulators (e.g., STAT1 and STAT3).
CONCLUSIONS: Exposure to alcohol may augment thymic atrophy by altering the activity of key inflammatory mediators, such as STAT family members and inflammatory cytokines. These findings provide insights into the signaling pathways and upstream regulators that underly alcohol-induced thymic atrophy during aging, suggesting that alcohol consumption could prepone thymic atrophy.
METHODS: F344 rats were given 3-day binge-ethanol (4.8 g/kg/day; 52% w/v; i.g.) and the thymus was collected and weighed. Molecular mechanisms underlying ethanol-induced thymic atrophy were investigated by network meta-analysis using the QIAGEN Ingenuity Pathway Analysis (IPA). The molecules associated with ethanol were identified from the QIAGEN Knowledge Base (QKB) and those associated with thymic atrophy were identified from QKB and Mouse Genome Informatics (MGI). Aging-mediated Differential Expression Genes (DEGs) from mouse thymocytes were obtained from the Gene Expression Omnibus (GEO) database (GSE132136). The relationship between the molecules and associated signaling pathways were studied using IPA.
RESULTS: Binge-ethanol decreased thymic weight in F344 rats. Our meta-analysis using IPA identified molecules commonly shared by ethanol and thymic atrophy through which simulation with ethanol increased thymic atrophy. We then obtained aging-mediated DEGs from the atrophied thymocytes. We found that ethanol contributed to thymic atrophy through modulation of the aging-mediated DEGs. Our network meta-analysis suggests that ethanol may augment thymic atrophy through increased expression of cytokines (e.g., IL-6, IL-17A and IL-33) along with their regulators (e.g., STAT1 and STAT3).
CONCLUSIONS: Exposure to alcohol may augment thymic atrophy by altering the activity of key inflammatory mediators, such as STAT family members and inflammatory cytokines. These findings provide insights into the signaling pathways and upstream regulators that underly alcohol-induced thymic atrophy during aging, suggesting that alcohol consumption could prepone thymic atrophy.
摘要：
背景：胸腺萎缩的特征是胸腺细胞丢失，破坏胸腺建筑，以及随后免疫受损的幼稚T细胞的减少。胸腺萎缩发生在衰老期间。包括酒精滥用在内的环境因素也会导致胸腺萎缩。尽管酒精滥用和胸腺萎缩有联系,潜在的机制还没有得到充分的研究。我们旨在确定衰老过程中酒精诱导胸腺萎缩的分子和信号通路。
方法:F344大鼠给予3天的狂饮乙醇(4.8g/kg/天;52%w/v;i.g.),收集胸腺并称重。使用QIAGENIngenuityPathwayAnalysis（IPA）通过网络荟萃分析研究了乙醇诱导的胸腺萎缩的分子机制。从QIAGEN知识库（QKB）中鉴定与乙醇相关的分子，从QKB和小鼠基因组信息学（MGI）中鉴定与胸腺萎缩相关的分子。来自小鼠胸腺细胞的衰老介导的差异表达基因(DEG)从基因表达综合(GEO)数据库(GSE132136)获得。使用IPA研究了分子与相关信号通路之间的关系。
结果：Binge-乙醇降低了F344大鼠的胸腺重量。我们使用IPA进行的荟萃分析确定了通常由乙醇和胸腺萎缩共享的分子，通过这种模拟，乙醇增加了胸腺萎缩。然后，我们从萎缩的胸腺细胞中获得了衰老介导的DEGs。我们发现乙醇通过调节衰老介导的DEGs导致胸腺萎缩。我们的网络荟萃分析表明，乙醇可能通过增加细胞因子的表达来增强胸腺萎缩(例如，IL-6、IL-17A和IL-33)以及它们的调节剂(例如，STAT1和STAT3)。
结论：暴露于酒精可能通过改变关键炎症介质的活性而增加胸腺萎缩，如STAT家族成员和炎性细胞因子。这些发现提供了对衰老过程中酒精诱导胸腺萎缩的信号通路和上游调节因子的见解，这表明饮酒可能会导致胸腺萎缩。
方法:F344大鼠给予3天的狂饮乙醇(4.8g/kg/天;52%w/v;i.g.),收集胸腺并称重。使用QIAGENIngenuityPathwayAnalysis（IPA）通过网络荟萃分析研究了乙醇诱导的胸腺萎缩的分子机制。从QIAGEN知识库（QKB）中鉴定与乙醇相关的分子，从QKB和小鼠基因组信息学（MGI）中鉴定与胸腺萎缩相关的分子。来自小鼠胸腺细胞的衰老介导的差异表达基因(DEG)从基因表达综合(GEO)数据库(GSE132136)获得。使用IPA研究了分子与相关信号通路之间的关系。
结果：Binge-乙醇降低了F344大鼠的胸腺重量。我们使用IPA进行的荟萃分析确定了通常由乙醇和胸腺萎缩共享的分子，通过这种模拟，乙醇增加了胸腺萎缩。然后，我们从萎缩的胸腺细胞中获得了衰老介导的DEGs。我们发现乙醇通过调节衰老介导的DEGs导致胸腺萎缩。我们的网络荟萃分析表明，乙醇可能通过增加细胞因子的表达来增强胸腺萎缩(例如，IL-6、IL-17A和IL-33)以及它们的调节剂(例如，STAT1和STAT3)。
结论：暴露于酒精可能通过改变关键炎症介质的活性而增加胸腺萎缩，如STAT家族成员和炎性细胞因子。这些发现提供了对衰老过程中酒精诱导胸腺萎缩的信号通路和上游调节因子的见解，这表明饮酒可能会导致胸腺萎缩。
