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Open AccessArticle

Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma

1
Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
2
Allergic Center, Kansai Medical University Hospital, Hirakata, Osaka 573-1010, Japan
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(2), 326; https://doi.org/10.3390/biom10020326
Received: 17 January 2020 / Revised: 13 February 2020 / Accepted: 14 February 2020 / Published: 18 February 2020
(This article belongs to the Special Issue Eosinophilic Inflammation)
Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is recognized as a refractory eosinophilic disorder characterized by both upper and lower airway inflammation. In some severe cases, disease control is poor, likely due to local steroid insensitivity. In this study, we focused on protein phosphatase 2A (PP2A), a key factor regulating glucocorticoid receptor (GR) nuclear translocation, and examined its association with local responses to corticosteroids in eosinophilic airway inflammation. Our results indicated reduced responses to corticosteroids in nasal epithelial cells from ECRS patients with asthma, which were also associated with decreased PP2A mRNA expression. Eosinophil peroxidase stimulates elevated PP2A phosphorylation levels, reducing PP2A protein expression and activity. In addition, mRNA levels of inflammatory mediators (TSLP, IL-25, IL-33, CCL4, CCL5, CCL11, and CCL26) associated with eosinophilic airway inflammation in epithelial cells were increased in nasal polyps (eosinophil-rich areas) compared with those in uncinate process tissues (eosinophil-poor areas) from the same patients. PP2A reduction by siRNA reduced GR nuclear translocation, whereas PP2A overexpression by plasmid transfection, or PP2A activation by formoterol, enhanced GR nuclear translocation. Collectively, our findings indicate that PP2A may represent a promising therapeutic target in refractory eosinophilic airway inflammation characterized by local steroid insensitivity. View Full-Text
Keywords: asthma; corticosteroid sensitivity; eosinophilic chronic rhinosinusitis; glucocorticoid receptor; protein phosphatase 2A asthma; corticosteroid sensitivity; eosinophilic chronic rhinosinusitis; glucocorticoid receptor; protein phosphatase 2A
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Kobayashi, Y.; Kanda, A.; Yun, Y.; Bui, D.V.; Suzuki, K.; Sawada, S.; Asako, M.; Iwai, H. Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma. Biomolecules 2020, 10, 326.

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