RETRACTED: The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells
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)....
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.793517/full |
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| author | Sang Hag Lee Sung Hoon Kang Mun Soo Han Ji Won Kwak Hyeon Geun Kim Tae Hoon Lee Da Bin Lee Tae Hoon Kim |
| author_facet | Sang Hag Lee Sung Hoon Kang Mun Soo Han Ji Won Kwak Hyeon Geun Kim Tae Hoon Lee Da Bin Lee Tae Hoon Kim |
| author_sort | Sang Hag Lee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e5fce1cea3004de29a9a4c6f1ffc0d4d |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e5fce1cea3004de29a9a4c6f1ffc0d4d2025-08-20T03:17:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.793517793517RETRACTED: The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial CellsSang Hag LeeSung Hoon KangMun Soo HanJi Won KwakHyeon Geun KimTae Hoon LeeDa Bin LeeTae Hoon KimEphA2 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.793517/fullephrinA1/ephA2 signalingchronic rhinosinusitis with nasal polypschronic rhinosinusitis without nasal polypstype I interferontype III interferoninterferon stimulated genes |
| spellingShingle | Sang Hag Lee Sung Hoon Kang Mun Soo Han Ji Won Kwak Hyeon Geun Kim Tae Hoon Lee Da Bin Lee Tae Hoon Kim RETRACTED: The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells Frontiers in Immunology ephrinA1/ephA2 signaling chronic rhinosinusitis with nasal polyps chronic rhinosinusitis without nasal polyps type I interferon type III interferon interferon stimulated genes |
| title | RETRACTED: The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells |
| title_full | RETRACTED: The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells |
| title_fullStr | RETRACTED: The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells |
| title_full_unstemmed | RETRACTED: The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells |
| title_short | RETRACTED: The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells |
| title_sort | retracted the expression of ephrina1 epha2 receptor increases in chronic rhinosinusitis and ephrina1 epha2 signaling affects rhinovirus induced innate immunity in human sinonasal epithelial cells |
| topic | ephrinA1/ephA2 signaling chronic rhinosinusitis with nasal polyps chronic rhinosinusitis without nasal polyps type I interferon type III interferon interferon stimulated genes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.793517/full |
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