Long-term and high dose dexamethasone injection decreases the expression of Immunoglobulin Heavy (Light) Chain Variable Region Genes (IGH(L)Vs) in the mouse spleen
Long-term and high dose dexamethasone injection decreases the expression of Immunoglobulin Heavy (Light) Chain Variable Region Genes (IGH(L)Vs) in the mouse spleen
复制标题
长期大剂量地塞米松注射降低小鼠脾脏中免疫球蛋白重（轻）链可变区基因（IGH(L)Vs）的表达
DOI：
10.1016/j.gene.2019.01.047
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发表时间：
2019
期刊：
影响因子：
3.5
通讯作者：
Xie Yajun
中科院分区：
文献类型：
--
作者：
Qi Yuanhui;Yi Qiying;Liu Yamin;Hu Yanxia;Ni Dongshen;Liu Jianing;Zhou Qin;Xie Yajun
糖皮质激素作为强效抗炎和免疫抑制剂已广泛应用于临床实践。然而，它们如何工作的根本机制仍然没有得到解决。在这里，我们使用RNA-set分析了连续腹腔注射地塞米松后成年小鼠脾脏基因表达。我们在对照组（注射0.9%NaCl）和地塞米松组中分别鉴定了13565个和13702个基因，其中12920个基因在两组中均有表达，但对照组中仅鉴定了645个基因，地塞米松组中仅鉴定了782个基因。在地塞米松注射组中，分别有101和67个基因下调和上调。其中，129个是编码基因，19个被鉴定为非编码基因或假基因，其余20个是TEC（有待实验证实）基因。基因本体论（GO）和KEGG通路分析显示，这些差异表达基因在大肠杆菌-细胞因子受体相互作用通路中高度富集，并且129个已鉴定的编码基因中的大多数参与免疫系统和细胞粘附相关过程。此外，地塞米松治疗组中系统性红斑狼疮、肾素-血管紧张素系统、脂肪消化吸收和甘油脂质代谢途径受到显著影响。对照组未见明显的信号通路富集。此外，20个免疫球蛋白重链或轻链可变区基因（IGH（L）Vs）在地塞米松注射组中下调。IGH（L）Vs编码免疫球蛋白重链可变区，决定抗体的多样性和特异性。我们无法确定地塞米松治疗后差异表达的19个非编码基因的功能。我们的研究结果表明，IGH（L）Vs和非编码基因的表达在地塞米松的抗炎和免疫抑制作用中起重要作用，并可开发为潜在的药物在临床实践中。
Glucocorticoid hormones have been widely used in clinical practice as potent anti-inflammatory and immunosuppressive agents. However, the underlying mechanisms of how they work remain unaddressed. Here, we used RNA-set to profile spleen gene expression in adult mice after consistent intraperitoneal injection of dexamethasone. We identified 13565 genes in control (injected with 0.9% NaCl) and 13702 genes in dexamethasone-injected group, 12920 genes were expressed in both, but 645 genes were identified only in control and 782 genes were identified only in the dexamethasone group. In the dexamethasone-injected group 101 and 67 genes were down-and up-regulated, respectively. Among these, 129 were coding genes, 19 were identified as non-coding genes or pseudogenes, and the remaining 20 were TEC (to be experimentally confirmed) genes. Gene ontology (GO) and KEGG pathway analysis revealed that the cytokine-cytokine receptor interaction pathway was highly enriched in these differentially expressed genes, and that a majority of the 129 identified coding genes were involved in immune system and cell adhesion-associated processes. Moreover, systemic lupus erythematosus, renin-angiotensin system, fat digestion and absorption, and glycerolipid metabolism pathways were significantly affected in the dexamethasone-treatment group. No obvious signaling pathway was enriched in the control group. Additionally, 20 immunoglobulin heavy or light chain variable region genes (IGH(L)Vs) were down regulated in the dexamethasone-injected group. IGH(L)Vs encode the variable region of immunoglobulin heavy chain and determine the diversity and specificity of antibodies. We were unable to determine the function of the 19 non-coding genes with differential expression following dexamethasone treatment. Our findings indicate that the expression of IGH(L)Vs and non-coding genes play an important role in the anti-inflammatory and immunosuppressive effects of dexamethasone and could be developed as potential agents in clinical practice.