PI3K, p38 and JAK/STAT signalling in bronchial tissue from patients with asthma following allergen challenge
| Autor: | Dave Singh, Anna Domènech, Isabel Ramis, Montserrat Miralpeix, Marta Calbet, Neus Prats, Thomas Southworth, Alan Bell, Sarah Mason |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Kinase Clinical Biochemistry JAK-STAT signalling medicine.disease_cause Phosphoinositide 3-kinase 03 medical and health sciences Allergen Bronchoscopy medicine Protein kinase A Asthma Eosinophil cationic protein business.industry Research Biochemistry (medical) lcsh:RM1-950 JAK-STAT signaling pathway p38 mitogen-activated protein kinase respiratory system Allergens medicine.disease Immunohistochemistry respiratory tract diseases 030104 developmental biology lcsh:Therapeutics. Pharmacology Immunology STAT protein Molecular Medicine JAK-STAT Signalling Janus kinase business |
| Zdroj: | Biomarker Research Biomarker Research, Vol 6, Iss 1, Pp 1-8 (2018) Southworth, T, Mason, S, Bell, A, Ramis, I, Calbet, M, Domenech, A, Prats, N, Miralpeix, M & Singh, D 2018, ' PI3K, p38 and JAK/STAT signalling in bronchial tissue from patients with asthma following allergen challenge. ', Biomarker Research, vol. 6, no. 14 . https://doi.org/10.1186/s40364-018-0128-9 |
| ISSN: | 2050-7771 |
| Popis: | BackgroundInhaled allergen challenges are often used to evaluate novel asthma treatments in early phase clinical trials. Current novel therapeutic targets in asthma include phosphoinositide 3-kinases (PI3K) delta and gamma, p38 mitogen-activated protein kinase (p38) and Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signalling pathways. The activation of these pathways following allergen exposure in atopic asthma patients it is not known.MethodsWe collected bronchial biopsies from 11 atopic asthma patients at baseline and after allergen challenge to investigate biomarkers of PI3K, p38 MAPK and JAK/STAT activation by immunohistochemistry. Cell counts and levels of eosinophil cationic protein and interleukin-5 were also assessed in sputum and bronchoalvelar lavage.ResultsBiopsies collected post-allergen had an increased percentage of epithelial cells expressing phospho-p38 (17.5 vs 25.6%, p = 0.04), and increased numbers of sub-epithelial cells expressing phospho-STAT5 (122.2 vs 540.6 cells/mm2, p = 0.01) and the PI3K marker phospho-ribosomal protein S6 (180.7 vs 777.3 cells/mm2, p = 0.005). Type 2 inflammation was increased in the airways post allergen, with elevated levels of eosinophils, interleukin-5 and eosinophil cationic protein.ConclusionsFuture clinical trials of novel kinase inhibitors could use the allergen challenge model in proof of concept studies, while employing these biomarkers to investigate pharmacological inhibition in the lungs. |
| Databáze: | OpenAIRE |
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