CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation
Eosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airwa...
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2024-12-01
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| author | Yoshiki Kobayashi Chu Hong Hanh Naoto Yagi Nhi Kieu Thi Le Yasutaka Yun Akihiro Shimamura Kenta Fukui Akitoshi Mitani Kensuke Suzuki Akira Kanda Hiroshi Iwai |
| author_facet | Yoshiki Kobayashi Chu Hong Hanh Naoto Yagi Nhi Kieu Thi Le Yasutaka Yun Akihiro Shimamura Kenta Fukui Akitoshi Mitani Kensuke Suzuki Akira Kanda Hiroshi Iwai |
| author_sort | Yoshiki Kobayashi |
| collection | DOAJ |
| description | Eosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airway inflammation. Although eosinophils are activated and coincubation with airway epithelial cells prolongs their survival, the interaction mechanism between eosinophils and epithelial cells is unclear. This study examined the effect of eosinophils on mucin glycoprotein 1 (MUC1), a member of membrane-bound mucin, in the airway epithelial cells, to elucidate the mechanisms of the eosinophil–airway epithelial cell interaction. Nasal polyp samples from patients with CRSwNP and BEAS-2B airway epithelial cells, coincubated with purified eosinophils, were stained with two MUC1 antibodies. To confirm the involvement of CCL4, an anti-CCL4 neutralizing antibody or recombinant CCL4 was used as needed. The immunofluorescence results revealed a negative correlation between the expression of full-length MUC1 and eosinophil count in nasal polyps. In BEAS-2B coincubated with eosinophils, full-length MUC1, but not the C-terminal domain, was reduced, and eosinophil survival was prolonged, which was concomitant with CCL4 increase, whereas the anti-CCL4 neutralizing antibody decreased these reactions. The survival of eosinophils that contacted recombinant MUC1 without the N-terminal domain was prolonged, and recombinant CCL4 increased the expression of metalloproteases. Increased CCL4 induces the contact between eosinophils and airway epithelial cells by shedding the MUC1 N-terminal domain and enhances eosinophil survival in eosinophilic airway inflammation. This novel mechanism may be a therapeutic target for difficult-to-treat eosinophilic airway inflammation. |
| format | Article |
| id | doaj-art-a25a32bee7ee4f6eae6beefe59e516d2 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-a25a32bee7ee4f6eae6beefe59e516d22025-01-10T13:16:18ZengMDPI AGCells2073-44092024-12-011413310.3390/cells14010033CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway InflammationYoshiki Kobayashi0Chu Hong Hanh1Naoto Yagi2Nhi Kieu Thi Le3Yasutaka Yun4Akihiro Shimamura5Kenta Fukui6Akitoshi Mitani7Kensuke Suzuki8Akira Kanda9Hiroshi Iwai10Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanThird Department of Internal Medicine, Kansai Medical University, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanAirway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, JapanEosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airway inflammation. Although eosinophils are activated and coincubation with airway epithelial cells prolongs their survival, the interaction mechanism between eosinophils and epithelial cells is unclear. This study examined the effect of eosinophils on mucin glycoprotein 1 (MUC1), a member of membrane-bound mucin, in the airway epithelial cells, to elucidate the mechanisms of the eosinophil–airway epithelial cell interaction. Nasal polyp samples from patients with CRSwNP and BEAS-2B airway epithelial cells, coincubated with purified eosinophils, were stained with two MUC1 antibodies. To confirm the involvement of CCL4, an anti-CCL4 neutralizing antibody or recombinant CCL4 was used as needed. The immunofluorescence results revealed a negative correlation between the expression of full-length MUC1 and eosinophil count in nasal polyps. In BEAS-2B coincubated with eosinophils, full-length MUC1, but not the C-terminal domain, was reduced, and eosinophil survival was prolonged, which was concomitant with CCL4 increase, whereas the anti-CCL4 neutralizing antibody decreased these reactions. The survival of eosinophils that contacted recombinant MUC1 without the N-terminal domain was prolonged, and recombinant CCL4 increased the expression of metalloproteases. Increased CCL4 induces the contact between eosinophils and airway epithelial cells by shedding the MUC1 N-terminal domain and enhances eosinophil survival in eosinophilic airway inflammation. This novel mechanism may be a therapeutic target for difficult-to-treat eosinophilic airway inflammation.https://www.mdpi.com/2073-4409/14/1/33airway epithelial cellbronchial asthmaCCL4chronic rhinosinusitis with nasal polypseosinophilic chronic rhinosinusitismucin glycoprotein 1 |
| spellingShingle | Yoshiki Kobayashi Chu Hong Hanh Naoto Yagi Nhi Kieu Thi Le Yasutaka Yun Akihiro Shimamura Kenta Fukui Akitoshi Mitani Kensuke Suzuki Akira Kanda Hiroshi Iwai CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation Cells airway epithelial cell bronchial asthma CCL4 chronic rhinosinusitis with nasal polyps eosinophilic chronic rhinosinusitis mucin glycoprotein 1 |
| title | CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation |
| title_full | CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation |
| title_fullStr | CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation |
| title_full_unstemmed | CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation |
| title_short | CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation |
| title_sort | ccl4 affects eosinophil survival via the shedding of the muc1 n terminal domain in airway inflammation |
| topic | airway epithelial cell bronchial asthma CCL4 chronic rhinosinusitis with nasal polyps eosinophilic chronic rhinosinusitis mucin glycoprotein 1 |
| url | https://www.mdpi.com/2073-4409/14/1/33 |
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