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Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model
Asthma is a chronic lung disease that causes airflow obstruction due to airway inflammation. However, its therapeutics remain inadequate. We previously reported that phospholipase D1 (PLD1) is a key enzyme involved in the production of pro-inflammatory cytokines in airway inflammation induced by the...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938051/ https://www.ncbi.nlm.nih.gov/pubmed/29717122 http://dx.doi.org/10.1038/s12276-018-0083-4 |
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author | Lee, Yun Young Lee, So Young Park, Shin-Young Choi, Hye-Jin Kim, Eung-Gook Han, Joong-Soo |
author_facet | Lee, Yun Young Lee, So Young Park, Shin-Young Choi, Hye-Jin Kim, Eung-Gook Han, Joong-Soo |
author_sort | Lee, Yun Young |
collection | PubMed |
description | Asthma is a chronic lung disease that causes airflow obstruction due to airway inflammation. However, its therapeutics remain inadequate. We previously reported that phospholipase D1 (PLD1) is a key enzyme involved in the production of pro-inflammatory cytokines in airway inflammation induced by the house dust mite allergen Dermatophagoides farinae 2 (Der f 2). We also revealed that PLD1 is specifically inactivated by AP180 (assembly protein, 180 kDa) and identified the PLD1-specific binding motif (TVTSP) of AP180. Therefore, the aims of this study were to develop a novel anti-asthmatic agent that could suppress airway inflammation by inhibiting PLD1 and examine its acute and chronic toxicity. We designed TAT-TVTSP, a PLD1-inhibitory peptide fused with a cell-penetrating peptide (CPP) delivery system. TAT-TVTSP was efficiently delivered to bronchial epithelial cells and significantly reduced Der f 2-induced PLD activation and Interleukin 13 (IL-13) production. Intranasally administered TAT-TVTSP was also efficiently transferred to airway tissues and ameliorated airway inflammation in a Der f 2-induced allergic asthma mouse model. Moreover, we investigated the safety of TAT-TVTSP as a therapeutic agent through single- and repeated-dose toxicity studies in a mouse model. Taken together, these results indicated that a PLD1-inhibitory peptide fused with a cell-penetrating peptide may be useful for treating allergic inflammatory asthma induced by house dust mites (HDMs). |
format | Online Article Text |
id | pubmed-5938051 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59380512018-05-15 Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model Lee, Yun Young Lee, So Young Park, Shin-Young Choi, Hye-Jin Kim, Eung-Gook Han, Joong-Soo Exp Mol Med Article Asthma is a chronic lung disease that causes airflow obstruction due to airway inflammation. However, its therapeutics remain inadequate. We previously reported that phospholipase D1 (PLD1) is a key enzyme involved in the production of pro-inflammatory cytokines in airway inflammation induced by the house dust mite allergen Dermatophagoides farinae 2 (Der f 2). We also revealed that PLD1 is specifically inactivated by AP180 (assembly protein, 180 kDa) and identified the PLD1-specific binding motif (TVTSP) of AP180. Therefore, the aims of this study were to develop a novel anti-asthmatic agent that could suppress airway inflammation by inhibiting PLD1 and examine its acute and chronic toxicity. We designed TAT-TVTSP, a PLD1-inhibitory peptide fused with a cell-penetrating peptide (CPP) delivery system. TAT-TVTSP was efficiently delivered to bronchial epithelial cells and significantly reduced Der f 2-induced PLD activation and Interleukin 13 (IL-13) production. Intranasally administered TAT-TVTSP was also efficiently transferred to airway tissues and ameliorated airway inflammation in a Der f 2-induced allergic asthma mouse model. Moreover, we investigated the safety of TAT-TVTSP as a therapeutic agent through single- and repeated-dose toxicity studies in a mouse model. Taken together, these results indicated that a PLD1-inhibitory peptide fused with a cell-penetrating peptide may be useful for treating allergic inflammatory asthma induced by house dust mites (HDMs). Nature Publishing Group UK 2018-05-01 /pmc/articles/PMC5938051/ /pubmed/29717122 http://dx.doi.org/10.1038/s12276-018-0083-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Article Lee, Yun Young Lee, So Young Park, Shin-Young Choi, Hye-Jin Kim, Eung-Gook Han, Joong-Soo Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model |
title | Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model |
title_full | Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model |
title_fullStr | Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model |
title_full_unstemmed | Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model |
title_short | Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model |
title_sort | therapeutic potential of a phospholipase d1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a der f 2-induced airway inflammation model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938051/ https://www.ncbi.nlm.nih.gov/pubmed/29717122 http://dx.doi.org/10.1038/s12276-018-0083-4 |
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