The effect of PU.1 knockdown on gene expression and function of mast cells.
The effect of PU.1 knockdown on gene expression and function of mast cells.
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DOI：
10.1038/s41598-018-19378-y
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发表时间：
2018-01-31
影响因子：
4.6
通讯作者：
Nishiyama C
中科院分区：
文献类型：
--
作者：
Oda Y;Kasakura K;Fujigaki I;Kageyama A;Okumura K;Ogawa H;Yashiro T;Nishiyama C
PU.1是造血细胞特异性转录因子。在本研究中，我们研究了PU.1在体外和体内小鼠肥大细胞（MC）的基因表达和功能中的作用。当PU.1 siRNA导入骨髓来源的MCs（BMMCs）时，IgE介导的活化作用降低，Syk和FcεRIβ mRNA水平显著降低。由于Syk基因的调控机制在很大程度上是未知的，我们进行了启动子分析，发现PU. 1通过直接结合到5′-非翻译区的顺式元件来反式激活Syk启动子。在小鼠树突状细胞和人MC中也观察到PU.1参与Syk启动子，表明PU.1和Syk之间的关系在哺乳动物和造血谱系中很常见。当在小鼠足垫中输注siRNA转染的BMMC后静脉内施用抗原时，足垫增厚被PU.1敲低显著抑制。最后，免疫调节剂泊马度胺的给药抑制了小鼠的被动全身过敏反应。总之，这些结果表明，PU.1敲低可能是一种有效的策略，用于预防MC介导的过敏性疾病。
PU.1 is a hematopoietic cell-specific transcription factor. In the current study, we investigated the role of PU.1 in the gene expression and the function of mouse mast cells (MCs) in vitro and in vivo. When PU.1 siRNA was introduced into bone marrow-derived MCs (BMMCs), IgE-mediated activation was reduced, and the Syk and FcεRIβ mRNA levels were significantly decreased. As the regulatory mechanism of the Syk gene is largely unknown, we performed promoter analysis and found that PU.1 transactivated the Syk promoter through direct binding to a cis-element in the 5′-untranslated region. The involvement of PU.1 in the Syk promoter was also observed in mouse dendritic cells and human MCs, suggesting that the relationship between PU.1 and Syk is common in mammals and in hematopoietic lineages. When antigen was administrated intravenously after the transfusion of siRNA-transfected BMMCs in the mouse footpad, the footpad thickening was significantly suppressed by PU.1 knockdown. Finally, administration of the immunomodulator pomalidomide suppressed passive systemic anaphylaxis of mice. Taken together, these results indicate that PU.1 knockdown might be an efficacious strategy for the prevention of MC-mediated allergic diseases.
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影响因子：
4.6
作者：
Yashiro T;Hara M;Ogawa H;Okumura K;Nishiyama C
通讯作者：
Nishiyama C
DOI：
10.4168/aair.2014.6.1.6
发表时间：
2014-01
期刊：
Allergy, asthma & immunology research
影响因子：
--
作者：
Kawakami T;Kashiwakura J;Kawakami Y
通讯作者：
Kawakami Y
影响因子：
3.7
作者：
Yashiro T;Kubo M;Ogawa H;Okumura K;Nishiyama C
通讯作者：
Nishiyama C
影响因子：
2.7
作者：
Kirshenbaum, AS;Akin, C;Metcalfe, DD
通讯作者：
Metcalfe, DD
影响因子：
20.3
作者：
Maeda, Keiko;Nishiyama, Chiharu;Ogawa, Hideoki
通讯作者：
Ogawa, Hideoki