Image_10_The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells.tif
EphA2 receptor and its ephrin ligands are involved in virus infection, epithelial permeability, and chemokine secretion. We hypothesized that ephrinA1/ephA2 signaling participates in rhinovirus (RV)-induced antiviral immune response in sinonasal mucosa of patients with chronic rhinosinusitis (CRS). Therefore, we investigated the expression of ephrinA1/ephA2 in normal and inflamed sinonasal mucosa and evaluated whether they regulate chemokine secretion and the production of antiviral immune mediators including interferons (IFNs) in RV-infected human primary sinonasal epithelial cells. For this purpose, the expression and distribution of ephrinA1/ephA2 in sinonasal mucosa were evaluated with RT-qPCR, immunofluorescence, and western blot. Their roles in chemokine secretion and the production of antiviral immune mediators such as type I and III IFNs, and interferon stimulated genes were evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to RV and poly(I:C). We found that ephrinA1/ephA2 were expressed in normal mucosa and their levels increased in inflamed sinonasal mucosa of CRS patients. RV infection or poly(I:C) treatment induced chemokine secretion which were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. The production of antiviral immune mediators enhanced by rhinovirus or poly (I:C) is increased by blocking ephA2 compared with that of cells stimulated by either rhinovirus or poly(I:C) alone. In addition, blocking ephA2 attenuated RV replication in cultured cells. Taken together, these results describe a novel role of ephrinA1/ephA2 signaling in antiviral innate immune response in sinonasal epithelium, suggesting their participation in RV-induced development and exacerbations of CRS.
History
References
- https://doi.org//10.4193/Rhino12.000
- https://doi.org//10.1002/alr.22403
- https://doi.org//10.1080/1744666X.2019.1601556
- https://doi.org//10.1111/all.13772
- https://doi.org//10.3389/fcimb.2019.00415
- https://doi.org//10.1007/s11882-017-0693-2
- https://doi.org//10.2500/105065898782102954
- https://doi.org//10.1097/00063198-200205000-00009
- https://doi.org//10.1016/j.cyto.2008.07.009
- https://doi.org//10.1164/rccm.200801-136OC
- https://doi.org//10.1002/lary.20764
- https://doi.org//10.1016/j.jaci.2019.08.010
- https://doi.org//10.1371/journal.pone.0098239
- https://doi.org//10.1093/infdis/jix640
- https://doi.org//10.1084/jem.20041901
- https://doi.org//10.1038/nm1462
- https://doi.org//10.3389/fcimb.2020.00277
- https://doi.org//10.3389/fimmu.2020.00974
- https://doi.org//10.1016/j.jaci.2018.04.003
- https://doi.org//10.1164/ajrccm.164.9.2105011
- https://doi.org//10.1074/jbc.M502879200
- https://doi.org//10.1146/annurev-pharmtox-011112-140226
- https://doi.org//10.1016/j.phrs.2012.10.008
- https://doi.org//10.3390/cells9020513
- https://doi.org//10.1038/s41564-017-0059-5
- https://doi.org//10.1038/s41564-017-0080-8
- https://doi.org//10.1073/pnas.1119592109
- https://doi.org//10.1038/nm.2805
- https://doi.org//10.3389/fimmu.2020.513383
- https://doi.org//10.1042/CS20160360
- https://doi.org//10.1152/ajpcell.00415.2012
- https://doi.org//10.1165/rcmb.2011-0044OC
- https://doi.org//10.1152/ajplung.90256.2008
- https://doi.org//10.1152/ajplung.00118.2009
- https://doi.org//10.5056/jnm19095
- https://doi.org//10.1111/all.12644
- https://doi.org//10.1016/s0194-5998(97)70005-6
- https://doi.org//10.1067/mhn.2002.121022
- https://doi.org//10.1016/s0194-5998(97)70001-9
- https://doi.org//10.1001/archinte.1958.00260140099015
- https://doi.org//10.1371/journal.pone.0114322
- https://doi.org//10.1016/B978-0-12-396456-4.00002-X
- https://doi.org//10.3748/wjg.v11.i29.4511
- https://doi.org//10.3748/wjg.v11.i26.4024
- https://doi.org//10.4161/19336918.2014.970012
- https://doi.org//10.1096/fj.04-3647fje
- https://doi.org//10.1161/ATVBAHA.111.242792
- https://doi.org//10.1074/jbc.M111.311670
- https://doi.org//10.1016/j.jaci.2010.04.021
- https://doi.org//10.1152/ajplung.00060.2007
- https://doi.org//10.1111/j.1365-2222.1997.tb00670.x
- https://doi.org//10.1016/j.cyto.2019.154798
- https://doi.org//10.1016/j.pharmthera.2004.07.007
- https://doi.org//10.1128/JVI.80.9.4501-4509.2006
- https://doi.org//10.1159/000484258
Usage metrics
Read the peer-reviewed publication
Categories
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity
CC BY 4.0