Anti-inflammatory potential of PI3Kδ and JAK inhibitors in asthma patients.
Respir Res
; 17(1): 124, 2016 10 04.
Article
en En
| MEDLINE
| ID: mdl-27716212
ABSTRACT
BACKGROUND:
Phosphatidylinositol 3-kinase delta (PI3Kδ) and Janus-activated kinases (JAK) are both novel anti-inflammatory targets in asthma that affect lymphocyte activation. We have investigated the anti-inflammatory effects of PI3Kδ and JAK inhibition on cytokine release from asthma bronchoalveolar lavage (BAL) cells and T-cell activation, and measured lung PI3Kδ and JAK signalling pathway expression.METHOD:
Cells isolated from asthma patients and healthy subjects were treated with PI3Kδ or JAK inhibitors, and/or dexamethasone, before T-cell receptor stimulation. Levels of IFNγ, IL-13 and IL-17 were measured by ELISA and flow cytometry was used to assess T-cell activation. PI3Kδ, PI3Kγ, phosphorylated protein kinase B (pAKT) and Signal Transducer and Activator of Transcription (STAT) protein expression were assessed by immunohistochemistry in bronchial biopsy tissue from asthma patients and healthy subjects. PI3Kδ expression in BAL CD3 cells was measured by flow cytometry.RESULTS:
JAK and PI3Kδ inhibitors reduced cytokine levels from both asthma and healthy BAL cells. Combining dexamethasone with either a JAK or PI3Kδ inhibitor showed an additive anti-inflammatory effect. JAK and PI3Kδ inhibitors were shown to have direct effects on T-cell activation. Immunohistochemistry showed increased numbers of PI3Kδ expressing cells in asthma bronchial tissue compared to controls. Asthma CD3 cells in BAL expressed higher levels of PI3Kδ protein compared to healthy cells.CONCLUSIONS:
Targeting PI3Kδ or JAK may prove effective in reducing T-cell activation and the resulting cytokine production in asthma.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piperidinas
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Pirimidinas
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Pirroles
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Asma
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Linfocitos T
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Quinasas Janus
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Fosfatidilinositol 3-Quinasa Clase I
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Inhibidores de las Cinasas Janus
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Pulmón
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Antiinflamatorios
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Respir Res
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido