Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells
Summary: The interactions between EPH receptors and ephrin (EFN) ligands play a crucial role in maintaining epithelial integrity and aiding in defense against infections. However, it remains unclear how the EPH-EFN trans-binding changes during infections and how this alteration affects inflammatory...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001324 |
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| author | Ryosuke Fukuda Shiori Beppu Daichi Hinata Yuka Kamada Tsukasa Okiyoneda |
| author_facet | Ryosuke Fukuda Shiori Beppu Daichi Hinata Yuka Kamada Tsukasa Okiyoneda |
| author_sort | Ryosuke Fukuda |
| collection | DOAJ |
| description | Summary: The interactions between EPH receptors and ephrin (EFN) ligands play a crucial role in maintaining epithelial integrity and aiding in defense against infections. However, it remains unclear how the EPH-EFN trans-binding changes during infections and how this alteration affects inflammatory response. Here we report that pathogen-associated molecular patterns (PAMPs) disrupt the EPHA2-EFNA1 trans-binding in airway epithelial cells (AECs). Mechanistically, flagellin induces the TLR5-dependent EFNA1 cleavage through the metalloproteinase ADAM9 concomitant with the activation of ligand-independent EPHA2 signaling. We found that the ablation of EPHA2 reduced the responsiveness of respiratory inflammation induced by flagellin and Pseudomonas aeruginosa both in vitro and in vivo. Notably, even in the absence of PAMPs, the inflammatory response in AECs was stimulated by forcibly induced EFNA1 shedding. These findings illustrate that the perturbation of the EPHA2-EFNA1 trans-binding acts as a sensing mechanism for infections and amplifies the inflammatory response, providing a defense mechanism for respiratory epithelia. |
| format | Article |
| id | doaj-art-2f2d63392db344dd814f0ba32e799d16 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-2f2d63392db344dd814f0ba32e799d162025-02-05T04:32:33ZengElsevieriScience2589-00422025-02-01282111872Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cellsRyosuke Fukuda0Shiori Beppu1Daichi Hinata2Yuka Kamada3Tsukasa Okiyoneda4Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Hyogo 669-1330, Japan; Corresponding authorDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Hyogo 669-1330, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Hyogo 669-1330, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Hyogo 669-1330, JapanDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, Hyogo 669-1330, JapanSummary: The interactions between EPH receptors and ephrin (EFN) ligands play a crucial role in maintaining epithelial integrity and aiding in defense against infections. However, it remains unclear how the EPH-EFN trans-binding changes during infections and how this alteration affects inflammatory response. Here we report that pathogen-associated molecular patterns (PAMPs) disrupt the EPHA2-EFNA1 trans-binding in airway epithelial cells (AECs). Mechanistically, flagellin induces the TLR5-dependent EFNA1 cleavage through the metalloproteinase ADAM9 concomitant with the activation of ligand-independent EPHA2 signaling. We found that the ablation of EPHA2 reduced the responsiveness of respiratory inflammation induced by flagellin and Pseudomonas aeruginosa both in vitro and in vivo. Notably, even in the absence of PAMPs, the inflammatory response in AECs was stimulated by forcibly induced EFNA1 shedding. These findings illustrate that the perturbation of the EPHA2-EFNA1 trans-binding acts as a sensing mechanism for infections and amplifies the inflammatory response, providing a defense mechanism for respiratory epithelia.http://www.sciencedirect.com/science/article/pii/S2589004225001324Biological sciencesBiochemistryCell biology |
| spellingShingle | Ryosuke Fukuda Shiori Beppu Daichi Hinata Yuka Kamada Tsukasa Okiyoneda Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells iScience Biological sciences Biochemistry Cell biology |
| title | Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells |
| title_full | Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells |
| title_fullStr | Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells |
| title_full_unstemmed | Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells |
| title_short | Perturbation of EPHA2 and EFNA1 trans binding amplifies inflammatory response in airway epithelial cells |
| title_sort | perturbation of epha2 and efna1 trans binding amplifies inflammatory response in airway epithelial cells |
| topic | Biological sciences Biochemistry Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001324 |
| work_keys_str_mv | AT ryosukefukuda perturbationofepha2andefna1transbindingamplifiesinflammatoryresponseinairwayepithelialcells AT shioribeppu perturbationofepha2andefna1transbindingamplifiesinflammatoryresponseinairwayepithelialcells AT daichihinata perturbationofepha2andefna1transbindingamplifiesinflammatoryresponseinairwayepithelialcells AT yukakamada perturbationofepha2andefna1transbindingamplifiesinflammatoryresponseinairwayepithelialcells AT tsukasaokiyoneda perturbationofepha2andefna1transbindingamplifiesinflammatoryresponseinairwayepithelialcells |