Vitamin D impedes eosinophil chemotaxis via inhibiting glycolysis-induced CCL26 expression in eosinophilic chronic rhinosinusitis with nasal polyps
Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is likely to relapse due to aberrant eosinophil infiltration. The deficiency of Vitamin D (VD) is associated with increased eosinophil infiltration in eosinophilic oesophagitis. However, the role of VD in eosinophilic CRSwNP (ECRS...
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BMC
2025-02-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02078-2 |
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| author | Weiqiang Huang Yana Zhang Yue Li Junming Ma Xia Li Yanjie Jiang Jianqi Wang Haotian Wu Xiaohong Chen Zizhen Huang Xifu Wu Xiaoping Lai Donglin Li Lihong Chang Gehua Zhang |
| author_facet | Weiqiang Huang Yana Zhang Yue Li Junming Ma Xia Li Yanjie Jiang Jianqi Wang Haotian Wu Xiaohong Chen Zizhen Huang Xifu Wu Xiaoping Lai Donglin Li Lihong Chang Gehua Zhang |
| author_sort | Weiqiang Huang |
| collection | DOAJ |
| description | Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is likely to relapse due to aberrant eosinophil infiltration. The deficiency of Vitamin D (VD) is associated with increased eosinophil infiltration in eosinophilic oesophagitis. However, the role of VD in eosinophilic CRSwNP (ECRSwNP) remains unclear. This study aims to explore the effects of VD on eosinophil chemotaxis in ECRSwNP and the underlying mechanisms. Methods Human nasal mucosal tissues were collected from the control group, patients with non-ECRSwNP and those with ECRSwNP. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of VD and CCL26 in the nasal mucosa, plasma, or human primary nasal epithelial cells (hNECs). hNECs and eosinophils from patients were cultured to investigate the effect of VD on eosinophil chemotaxis and CCL26 expression via eosinophil migration assay, Western blot, and ELISA. Transcriptome sequencing, pathway enrichment analysis, Western blot and immunohistochemical staining were used to determine the key signaling pathway involved in eosinophil chemotaxis. Results A significant decrease in VD levels was observed in the nasal mucosa of patients with ECRSwNP, which correlated with increased local eosinophil infiltration. Furthermore, pathway enrichment analysis suggested that glycolysis signaling was promoted in the ECRSwNP group, verified by enhanced expression of glycolytic key enzymes that were positively correlated with eosinophil infiltration in nasal mucosa from patients with ECRSwNP. VD suppressed eosinophil chemotaxis in vitro by inhibiting CCL26 expression. Glycolysis regulated CCL26 expression via the ERK pathway and lactate, which promoted the expression and stability of CCL26 protein. VD attenuated glycolysis, leading to decreased production of lactate and inactivation of the ERK pathway. The decrease in lactate production suppressed eosinophil chemotaxis. Moreover, the ERK pathway activator reversed the inhibitory effect of VD on eosinophil chemotaxis. Conclusions VD impedes eosinophil chemotaxis by inhibiting glycolysis - induced CCL26 expression via attenuating the activation of the ERK pathway and reducing lactate production. VD supplementation may be a novel strategy to treat ECRSwNP. |
| format | Article |
| id | doaj-art-bf54383e92d34274a0ef490d8e06992c |
| institution | DOAJ |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-bf54383e92d34274a0ef490d8e06992c2025-08-20T03:13:12ZengBMCCell Communication and Signaling1478-811X2025-02-0123111610.1186/s12964-025-02078-2Vitamin D impedes eosinophil chemotaxis via inhibiting glycolysis-induced CCL26 expression in eosinophilic chronic rhinosinusitis with nasal polypsWeiqiang Huang0Yana Zhang1Yue Li2Junming Ma3Xia Li4Yanjie Jiang5Jianqi Wang6Haotian Wu7Xiaohong Chen8Zizhen Huang9Xifu Wu10Xiaoping Lai11Donglin Li12Lihong Chang13Gehua Zhang14Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen UniversityAbstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is likely to relapse due to aberrant eosinophil infiltration. The deficiency of Vitamin D (VD) is associated with increased eosinophil infiltration in eosinophilic oesophagitis. However, the role of VD in eosinophilic CRSwNP (ECRSwNP) remains unclear. This study aims to explore the effects of VD on eosinophil chemotaxis in ECRSwNP and the underlying mechanisms. Methods Human nasal mucosal tissues were collected from the control group, patients with non-ECRSwNP and those with ECRSwNP. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of VD and CCL26 in the nasal mucosa, plasma, or human primary nasal epithelial cells (hNECs). hNECs and eosinophils from patients were cultured to investigate the effect of VD on eosinophil chemotaxis and CCL26 expression via eosinophil migration assay, Western blot, and ELISA. Transcriptome sequencing, pathway enrichment analysis, Western blot and immunohistochemical staining were used to determine the key signaling pathway involved in eosinophil chemotaxis. Results A significant decrease in VD levels was observed in the nasal mucosa of patients with ECRSwNP, which correlated with increased local eosinophil infiltration. Furthermore, pathway enrichment analysis suggested that glycolysis signaling was promoted in the ECRSwNP group, verified by enhanced expression of glycolytic key enzymes that were positively correlated with eosinophil infiltration in nasal mucosa from patients with ECRSwNP. VD suppressed eosinophil chemotaxis in vitro by inhibiting CCL26 expression. Glycolysis regulated CCL26 expression via the ERK pathway and lactate, which promoted the expression and stability of CCL26 protein. VD attenuated glycolysis, leading to decreased production of lactate and inactivation of the ERK pathway. The decrease in lactate production suppressed eosinophil chemotaxis. Moreover, the ERK pathway activator reversed the inhibitory effect of VD on eosinophil chemotaxis. Conclusions VD impedes eosinophil chemotaxis by inhibiting glycolysis - induced CCL26 expression via attenuating the activation of the ERK pathway and reducing lactate production. VD supplementation may be a novel strategy to treat ECRSwNP.https://doi.org/10.1186/s12964-025-02078-2Eosinophilic chronic rhinosinusitis with nasal polypsEosinophil chemotaxisVitamin DGlycolysisLactateCCL26 |
| spellingShingle | Weiqiang Huang Yana Zhang Yue Li Junming Ma Xia Li Yanjie Jiang Jianqi Wang Haotian Wu Xiaohong Chen Zizhen Huang Xifu Wu Xiaoping Lai Donglin Li Lihong Chang Gehua Zhang Vitamin D impedes eosinophil chemotaxis via inhibiting glycolysis-induced CCL26 expression in eosinophilic chronic rhinosinusitis with nasal polyps Cell Communication and Signaling Eosinophilic chronic rhinosinusitis with nasal polyps Eosinophil chemotaxis Vitamin D Glycolysis Lactate CCL26 |
| title | Vitamin D impedes eosinophil chemotaxis via inhibiting glycolysis-induced CCL26 expression in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_full | Vitamin D impedes eosinophil chemotaxis via inhibiting glycolysis-induced CCL26 expression in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_fullStr | Vitamin D impedes eosinophil chemotaxis via inhibiting glycolysis-induced CCL26 expression in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_full_unstemmed | Vitamin D impedes eosinophil chemotaxis via inhibiting glycolysis-induced CCL26 expression in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_short | Vitamin D impedes eosinophil chemotaxis via inhibiting glycolysis-induced CCL26 expression in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_sort | vitamin d impedes eosinophil chemotaxis via inhibiting glycolysis induced ccl26 expression in eosinophilic chronic rhinosinusitis with nasal polyps |
| topic | Eosinophilic chronic rhinosinusitis with nasal polyps Eosinophil chemotaxis Vitamin D Glycolysis Lactate CCL26 |
| url | https://doi.org/10.1186/s12964-025-02078-2 |
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