Distinct Roles Between Eotaxin 1 and Eotaxin 2 in Asthmatic Airways
ABSTRACT Background Eotaxins (EOTs), primarily expressed in airway epithelial cells (AECs), act as chemoattractants for eosinophils in asthma pathogenesis. Recent studies have suggested that EOTs have additional functions beyond chemotaxis. However, the distinct roles of EOTs remain incompletely und...
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Wiley
2025-07-01
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| Series: | Clinical and Translational Allergy |
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| Online Access: | https://doi.org/10.1002/clt2.70077 |
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| author | Soyoon Sim Eun‐mi Yang Yoo Seob Shin Seon Beom Kim Youngwoo Choi Hae‐Sim Park |
| author_facet | Soyoon Sim Eun‐mi Yang Yoo Seob Shin Seon Beom Kim Youngwoo Choi Hae‐Sim Park |
| author_sort | Soyoon Sim |
| collection | DOAJ |
| description | ABSTRACT Background Eotaxins (EOTs), primarily expressed in airway epithelial cells (AECs), act as chemoattractants for eosinophils in asthma pathogenesis. Recent studies have suggested that EOTs have additional functions beyond chemotaxis. However, the distinct roles of EOTs remain incompletely understood. Methods Serum EOT1, EOT2, myeloperoxidase (MPO), matrix metalloproteinase‐9 (MMP‐9), and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) levels were evaluated by ELISA and serum eosinophil cationic protein (ECP) levels were measured by ImmunoCAP in 79 adult asthmatics. Clinical characteristics were analyzed by inflammatory phenotype, disease severity, and serum EOT1/EOT2 levels. The functions of EOTs were investigated in vitro and ex vivo. For in vivo, EOT1 and EOT2 were intranasally administered to ovalbumin/lipopolysaccharide‐induced asthmatic mice (BALB/c). To assess neutralization effects, anti‐EOT1 or anti‐EOT2 antibodies were intranasally administered. Results Serum EOT1 and EOT2 levels were higher in patients with severe asthma (SA) than in those with non‐SA. Serum EOT1 levels were associated with increased blood/sputum eosinophil counts and serum ECP levels, but not significantly correlated with FEV1 (%) values. In contrast, serum EOT2 levels are correlated with higher serum MPO, MMP‐9, and TIMP‐1 levels but lower FEV1 (%). In asthmatic mice, EOT1 increased eosinophil counts and IL‐5 production, whereas EOT2 induced CXCL1 and MMP‐9 production, junctional dysfunction and epithelial‐to‐mesenchymal transition in the lungs, which were attenuated by neutralizing EOTs using each antibody. Conclusion EOT1 promotes T2/eosinophilic inflammation, whereas EOT2 accelerates airway remodeling and lung function decline by activating neutrophils, providing a new insight into the distinct roles of EOTs in the pathogenesis of SA. |
| format | Article |
| id | doaj-art-7d61b09f708145d2bda67554de0623d2 |
| institution | Kabale University |
| issn | 2045-7022 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
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| series | Clinical and Translational Allergy |
| spelling | doaj-art-7d61b09f708145d2bda67554de0623d22025-08-20T03:41:58ZengWileyClinical and Translational Allergy2045-70222025-07-01157n/an/a10.1002/clt2.70077Distinct Roles Between Eotaxin 1 and Eotaxin 2 in Asthmatic AirwaysSoyoon Sim0Eun‐mi Yang1Yoo Seob Shin2Seon Beom Kim3Youngwoo Choi4Hae‐Sim Park5Department of Allergy and Clinical Immunology Ajou University School of Medicine Suwon KoreaDepartment of Allergy and Clinical Immunology Ajou University School of Medicine Suwon KoreaDepartment of Allergy and Clinical Immunology Ajou University School of Medicine Suwon KoreaDepartment of Food Science and Technology Pusan National University Miryang KoreaDepartment of Biomaterials Science (BK21 FOUR Program) College of Natural Resources and Life Science Life and Industry Convergence Research Institute Pusan National University Miryang KoreaDepartment of Allergy and Clinical Immunology Ajou University School of Medicine Suwon KoreaABSTRACT Background Eotaxins (EOTs), primarily expressed in airway epithelial cells (AECs), act as chemoattractants for eosinophils in asthma pathogenesis. Recent studies have suggested that EOTs have additional functions beyond chemotaxis. However, the distinct roles of EOTs remain incompletely understood. Methods Serum EOT1, EOT2, myeloperoxidase (MPO), matrix metalloproteinase‐9 (MMP‐9), and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) levels were evaluated by ELISA and serum eosinophil cationic protein (ECP) levels were measured by ImmunoCAP in 79 adult asthmatics. Clinical characteristics were analyzed by inflammatory phenotype, disease severity, and serum EOT1/EOT2 levels. The functions of EOTs were investigated in vitro and ex vivo. For in vivo, EOT1 and EOT2 were intranasally administered to ovalbumin/lipopolysaccharide‐induced asthmatic mice (BALB/c). To assess neutralization effects, anti‐EOT1 or anti‐EOT2 antibodies were intranasally administered. Results Serum EOT1 and EOT2 levels were higher in patients with severe asthma (SA) than in those with non‐SA. Serum EOT1 levels were associated with increased blood/sputum eosinophil counts and serum ECP levels, but not significantly correlated with FEV1 (%) values. In contrast, serum EOT2 levels are correlated with higher serum MPO, MMP‐9, and TIMP‐1 levels but lower FEV1 (%). In asthmatic mice, EOT1 increased eosinophil counts and IL‐5 production, whereas EOT2 induced CXCL1 and MMP‐9 production, junctional dysfunction and epithelial‐to‐mesenchymal transition in the lungs, which were attenuated by neutralizing EOTs using each antibody. Conclusion EOT1 promotes T2/eosinophilic inflammation, whereas EOT2 accelerates airway remodeling and lung function decline by activating neutrophils, providing a new insight into the distinct roles of EOTs in the pathogenesis of SA.https://doi.org/10.1002/clt2.70077airway epithelial cellsairway remodelingasthmaeosinophilseotaxinneutrophils |
| spellingShingle | Soyoon Sim Eun‐mi Yang Yoo Seob Shin Seon Beom Kim Youngwoo Choi Hae‐Sim Park Distinct Roles Between Eotaxin 1 and Eotaxin 2 in Asthmatic Airways Clinical and Translational Allergy airway epithelial cells airway remodeling asthma eosinophils eotaxin neutrophils |
| title | Distinct Roles Between Eotaxin 1 and Eotaxin 2 in Asthmatic Airways |
| title_full | Distinct Roles Between Eotaxin 1 and Eotaxin 2 in Asthmatic Airways |
| title_fullStr | Distinct Roles Between Eotaxin 1 and Eotaxin 2 in Asthmatic Airways |
| title_full_unstemmed | Distinct Roles Between Eotaxin 1 and Eotaxin 2 in Asthmatic Airways |
| title_short | Distinct Roles Between Eotaxin 1 and Eotaxin 2 in Asthmatic Airways |
| title_sort | distinct roles between eotaxin 1 and eotaxin 2 in asthmatic airways |
| topic | airway epithelial cells airway remodeling asthma eosinophils eotaxin neutrophils |
| url | https://doi.org/10.1002/clt2.70077 |
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