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首页> 外文期刊>Journal of land use science >Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms
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Genomic and transcriptomic comparison of allergen and silver nanoparticle-induced mast cell degranulation reveals novel non-immunoglobulin E mediated mechanisms

机译：过敏原和银纳米粒子诱导的肥大细胞脱溶的基因组和转录组比较揭示了新型非免疫球蛋白E介导机制

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摘要

Mast cells represent a crucial cell type in host defense; however, maladaptive responses are contributing factors in the pathogenesis of allergic diseases. Previous work in our laboratory has shown that exposure to silver nanoparticles (AgNPs) results in mast cell degranulation via a non-immunoglobulin E (IgE) mechanism. In this study, we utilized a systems biology approach to identify novel genetic factors playing a role in AgNP-induced mast cell degranulation compared to the classical activation by antigen-mediated FccRl crosslinking. Mast cell degranulation was assessed in bone marrow-derived mast cells isolated from 23 strains of mice following exposure to AgNPs or FccRl crosslinking with dinitrophenyl (DNP). Utilizing strain-dependent mast cell degranulation, an association mapping study identified 3 chromosomal regions that were significantly associated with mast cell degranulation by AgNP and one non-overlapping region associated with DNP-mediated degranulation. Two of the AgNP-associated regions correspond to genes previously reported to be associated with allergic disorders (Trac2 on chromosome 1 and Traf6 on chromosome 2) and an uncharacterized gene identified on chromosome 1 (Fam126b). In conjunction, RNA-sequencing performed on mast cells from the high and low responder strains revealed 3754 and 34 differentially expressed genes that were unique to DNP and AgNP exposures, respectively. Select candidate genes include Ptger4, a gene encoding a G-protein coupled receptor in addition to a multifunctional adaptor protein, Txnip, that may be driving mast cell degranulation by AgNP. Taken together, we identified novel genes that have not been previously shown to play a role in nanoparticle-mediated mast cell activation. With further functional evaluation in the future, these genes may be potential therapeutic targets in the treatment of non-IgE mediated mast cell-linked disorders.
机译：肥大细胞代表主机防御中的关键细胞类型;然而，适应性反应是过敏性疾病发病机制的贡献因素。我们实验室的先前工作表明，暴露于银纳米颗粒（AGNP）导致肥大细胞通过非免疫球蛋白E（IgE）机制脱粒。在这项研究中，我们利用系统生物学方法来识别与抗原介导的FCCR1交联的经典活化相比，在AgNP诱导的肥大细胞脱粒中发挥作用的新遗传因素。在暴露于AgNPS或Fccrl交联后，在与二硝基苯（DNP）暴露于AgNP或Fccrl交联后，在骨髓衍生的肥大菌细胞中评估肥大细胞溶解。利用应变依赖性肥大细胞脱粒，缔解映射研究确定了3种染色体区域，其通过AgNP和与DNP介导的脱粒相关的一个非重叠区域显着与肥大细胞脱滴相关。两种AgNP相关区域对应于先前据报道的基因与过敏性疾病（Trac2上的Trac2和染色体2上的Traf6）和染色体1（FAM126B）上鉴定的非特征基因相关联。同时，在来自高响应者菌株和低响应菌株的肥大细胞上进行的RNA测序揭示了3754和34个差异表达的基因，其分别是DNP和AGNP暴露的差异。选择候选基因包括除了多功能适配器蛋白，TXNIP之外，编码G蛋白偶联受体的基因，其可以是通过AGNP驱动肥大细胞脱粒。一起携带，我们确定了尚未显示出在纳米粒子介导的肥大细胞活化中起作用的新基因。在未来进一步的功能评估中，这些基因可能是治疗非IGE介导的肥大细胞连接疾病的潜在治疗靶标。

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  • 来源
    《Journal of land use science》 |2018年第3期|共23页
  • 作者

    Johnson Monica; Alsaleh Nasser; Mendoza Ryan P.; Persaud Indushekhar; Bauer Alison K.; Saba Laura; Brown Jared M.;

  • 作者单位

    Univ Colorado Skaggs Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Aurora CO 80045 USA;

    Univ Colorado Skaggs Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Aurora CO 80045 USA;

    Univ Colorado Skaggs Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Aurora CO 80045 USA;

    Univ Colorado Skaggs Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Aurora CO 80045 USA;

    Univ Colorado Colorado Sch Publ Hlth Dept Environm &

    Occupat Hlth Aurora CO USA;

    Univ Colorado Skaggs Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Aurora CO 80045 USA;

    Univ Colorado Skaggs Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Aurora CO 80045 USA;

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  • 正文语种 eng
  • 中图分类 地球物理学;
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