The RNA-binding protein Mex-3B plays critical roles in the development of steroid-resistant neutrophilic airway inflammation
The RNA-binding protein Mex-3B plays critical roles in the development of steroid-resistant neutrophilic airway inflammation
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RNA结合蛋白Mex-3B在类固醇抵抗性中性粒细胞气道炎症的发展中发挥关键作用
DOI：
10.1016/j.bbrc.2019.08.158
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发表时间：
2019
影响因子：
3.1
通讯作者：
Akiyama Tetsu
中科院分区：
文献类型：
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作者：
Yamazumi Yusuke;Sasaki Oh;Suyama-Fuchino Saki;Kohu Kazuyoshi;Kamoshida Yuki;Harada Hiroaki;Fujio Keishi;Oda Takeaki;Akiyama Tetsu
虽然大多数哮喘可以用类固醇治疗，但约10%的严重哮喘对类固醇无效。最近的研究表明，在严重哮喘病例的亚组中，浸润到气道中的中性粒细胞在炎症中起重要作用。然而，这种增加的中性粒细胞浸润的机制还不清楚。在这里，使用类固醇耐药嗜中性粒细胞炎症的小鼠模型，我们表明，RNA结合蛋白Mex-3B缺陷的小鼠在气道中的中性粒细胞浸润比野生型小鼠显着减少。我们进一步证明，Mex-3B转录后上调CXCL 2，趋化因子，诱导中性粒细胞趋化性和迁移。此外，我们表明，无论是抗CXCL 2抗体或抗Mex-3B反义寡核苷酸治疗抑制嗜酸性过敏性气道炎症。这些结果表明，Mex-3B介导的CXCL 2诱导是类固醇耐药嗜酸性过敏性气道炎症的关键。我们的研究结果为激素抵抗型严重哮喘的治疗干预提供了新的策略。
While most asthma can be treated with steroids, about 10%, called severe asthma, is refractory to steroids. It has recently been shown that in a subgroup of severe asthma cases, neutrophils that infiltrate into the airways play an important role in inflammation. However, the mechanisms underlying this increased neutrophil infiltration are not well understood. Here, using a mouse model of steroid-resistant neutrophilic inflammation, we show that mice deficient for the RNA-binding protein Mex-3B have significantly less neutrophil infiltration in the airways than wild-type mice. We further demonstrate that Mex-3B post-transcriptionally upregulates CXCL2, a chemokine that induces neutrophil chemotaxis and migration. Moreover, we show that treatment with either anti-CXCL2 antibody or anti-Mex-3B antisense oligonucleotide suppresses neutrophilic allergic airway inflammation. These results suggest that Mex-3B-mediated induction of CXCL2 is crucial for steroid-resistant neutrophilic allergic airway inflammation. Our findings suggest new strategies for therapeutic intervention in steroid-resistant severe asthma.