Activation of Eosinophils Interacting with Bronchial Epithelial Cells by Antimicrobial Peptide LL-37: Implications in Allergic Asthma
Abstract The role of antimicrobial peptide LL-37 in asthma exacerbation is unclear. Microbial infection, which is the most common inducer of asthma exacerbation, is accompanied by elevated LL-37. The present study found that co-culture of eosinophils and bronchial epithelial cell line BEAS-2B signif...
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-02085-5 |
| _version_ | 1818752382357471232 |
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| author | Delong Jiao Chun-Kwok Wong Miranda Sin-Man Tsang Ida Miu-Ting Chu Dehua Liu Jing Zhu Man Chu Christopher Wai-Kei Lam |
| author_facet | Delong Jiao Chun-Kwok Wong Miranda Sin-Man Tsang Ida Miu-Ting Chu Dehua Liu Jing Zhu Man Chu Christopher Wai-Kei Lam |
| author_sort | Delong Jiao |
| collection | DOAJ |
| description | Abstract The role of antimicrobial peptide LL-37 in asthma exacerbation is unclear. Microbial infection, which is the most common inducer of asthma exacerbation, is accompanied by elevated LL-37. The present study found that co-culture of eosinophils and bronchial epithelial cell line BEAS-2B significantly enhanced intercellular adhesion molecule-1 on both cells and CD18 expression on eosinophils upon LL-37 stimulation. IL-6, CXCL8 and CCL4 were substantially released in co-culture in the presence of LL-37. LL-37 triggered the activation of eosinophils interacting with BEAS-2B cells in a P2X purinoceptor 7/epidermal growth factor receptor-dependent manner. Eosinophils and BEAS-2B cells differentially contribute to the expression of cytokines/chemokines in co-culture, while soluble mediators were sufficient to mediate the intercellular interactions. Intracellular p38-mitogen-activated protein kinase, extracellular signal-regulated kinase and NF-κB signaling pathways were essential for LL-37-mediated activation of eosinophils and BEAS-2B cells. By using the ovalbumin-induced asthmatic model, intranasal administration of mCRAMP (mouse ortholog of LL-37) in combination with ovalbumin during the allergen challenge stage significantly enhanced airway hyperresponsiveness and airway inflammation in sensitized mice, thereby implicating a deteriorating role of LL-37 in allergic asthma. This study provides evidence of LL-37 in triggering asthma exacerbation via the activation of eosinophils interacting with bronchial epithelial cells in inflammatory airway. |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:50:34Z |
| publishDate | 2017-05-01 |
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| series | Scientific Reports |
| spelling | doaj.art-d60f58a76dd14851a622ad620b0b38352022-12-21T21:20:27ZengNature PortfolioScientific Reports2045-23222017-05-017111310.1038/s41598-017-02085-5Activation of Eosinophils Interacting with Bronchial Epithelial Cells by Antimicrobial Peptide LL-37: Implications in Allergic AsthmaDelong Jiao0Chun-Kwok Wong1Miranda Sin-Man Tsang2Ida Miu-Ting Chu3Dehua Liu4Jing Zhu5Man Chu6Christopher Wai-Kei Lam7Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales HospitalInstitute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, the Chinese University of Hong KongDepartment of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales HospitalInstitute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, the Chinese University of Hong KongDepartment of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales HospitalDepartment of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales HospitalState Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and TechnologyAbstract The role of antimicrobial peptide LL-37 in asthma exacerbation is unclear. Microbial infection, which is the most common inducer of asthma exacerbation, is accompanied by elevated LL-37. The present study found that co-culture of eosinophils and bronchial epithelial cell line BEAS-2B significantly enhanced intercellular adhesion molecule-1 on both cells and CD18 expression on eosinophils upon LL-37 stimulation. IL-6, CXCL8 and CCL4 were substantially released in co-culture in the presence of LL-37. LL-37 triggered the activation of eosinophils interacting with BEAS-2B cells in a P2X purinoceptor 7/epidermal growth factor receptor-dependent manner. Eosinophils and BEAS-2B cells differentially contribute to the expression of cytokines/chemokines in co-culture, while soluble mediators were sufficient to mediate the intercellular interactions. Intracellular p38-mitogen-activated protein kinase, extracellular signal-regulated kinase and NF-κB signaling pathways were essential for LL-37-mediated activation of eosinophils and BEAS-2B cells. By using the ovalbumin-induced asthmatic model, intranasal administration of mCRAMP (mouse ortholog of LL-37) in combination with ovalbumin during the allergen challenge stage significantly enhanced airway hyperresponsiveness and airway inflammation in sensitized mice, thereby implicating a deteriorating role of LL-37 in allergic asthma. This study provides evidence of LL-37 in triggering asthma exacerbation via the activation of eosinophils interacting with bronchial epithelial cells in inflammatory airway.https://doi.org/10.1038/s41598-017-02085-5 |
| spellingShingle | Delong Jiao Chun-Kwok Wong Miranda Sin-Man Tsang Ida Miu-Ting Chu Dehua Liu Jing Zhu Man Chu Christopher Wai-Kei Lam Activation of Eosinophils Interacting with Bronchial Epithelial Cells by Antimicrobial Peptide LL-37: Implications in Allergic Asthma Scientific Reports |
| title | Activation of Eosinophils Interacting with Bronchial Epithelial Cells by Antimicrobial Peptide LL-37: Implications in Allergic Asthma |
| title_full | Activation of Eosinophils Interacting with Bronchial Epithelial Cells by Antimicrobial Peptide LL-37: Implications in Allergic Asthma |
| title_fullStr | Activation of Eosinophils Interacting with Bronchial Epithelial Cells by Antimicrobial Peptide LL-37: Implications in Allergic Asthma |
| title_full_unstemmed | Activation of Eosinophils Interacting with Bronchial Epithelial Cells by Antimicrobial Peptide LL-37: Implications in Allergic Asthma |
| title_short | Activation of Eosinophils Interacting with Bronchial Epithelial Cells by Antimicrobial Peptide LL-37: Implications in Allergic Asthma |
| title_sort | activation of eosinophils interacting with bronchial epithelial cells by antimicrobial peptide ll 37 implications in allergic asthma |
| url | https://doi.org/10.1038/s41598-017-02085-5 |
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