Epithelial–Immune Cell Interactions for Drug Discovery in Chronic Obstructive Pulmonary Disease
| Autor: | Joshua R. Chartock, Shamus P. Keeler, Kangyun Wu, Xinyu Wang, Derek E. Byers, Arthur G. Romero, Michael J. Holtzman, Benjamin J. Gerovac |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Exacerbation Cell Gene Expression Cell Communication Respiratory Mucosa Mucin 5AC 03 medical and health sciences Mitogen-Activated Protein Kinase 13 Pulmonary Disease Chronic Obstructive 0302 clinical medicine Immune system Drug Discovery medicine Animals Humans Protein kinase A Marvin I. Schwarz Lecture Endothelial Progenitor Cells Inflammation COPD Innate immune system Interleukin-13 business.industry Mucin respiratory system medicine.disease Immunity Innate respiratory tract diseases 030104 developmental biology medicine.anatomical_structure 030228 respiratory system Immunology business Airway Signal Transduction |
| Popis: | New studies of chronic obstructive pulmonary disease (COPD) are revealing the key role of airway epithelial cells and innate immune cells in the initiation, exacerbation, and progression of airway disease. An emerging scheme focuses on expansion of airway progenitor epithelial cells that feed forward for a type 2 immune response and consequent IL-13-driven mucus production that is linked to the morbidity and mortality of COPD. Analysis of human airway progenitor epithelial cells and airway tissue shows that IL-13 signaling to MUC5AC mucin gene expression relies on specific activation of mitogen-activated protein kinase 13, providing a druggable target for attenuating mucus production in the setting of viral infection and other inhaled stimuli of airway inflammation. Moreover, structure-based drug design is delivering highly potent, selective, and nontoxic small-molecule kinase inhibitors of mitogen-activated protein kinase 13 that offer a therapeutic strategy to downregulate excess mucus production to a physiological level and thereby achieve a precision medicine solution to the major health care problem of COPD and related airway diseases. |
| Databáze: | OpenAIRE |
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