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Publication : The RNA-binding protein Mex-3B plays critical roles in the development of steroid-resistant neutrophilic airway inflammation.

First Author  Yamazumi Y Year  2019
Journal  Biochem Biophys Res Commun Volume  519
Issue  2 Pages  220-226
PubMed ID  31493864 Mgi Jnum  J:292038
Mgi Id  MGI:6443763 Doi  10.1016/j.bbrc.2019.08.158
Citation  Yamazumi Y, et al. (2019) The RNA-binding protein Mex-3B plays critical roles in the development of steroid-resistant neutrophilic airway inflammation. Biochem Biophys Res Commun 519(2):220-226
abstractText  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.
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