Inhibition of histone-deacetylase activity rescues inflammatory cystic fibrosis lung disease by modulating innate and adaptive immune responses
| Autor: | Manish Bodas, Taehong Min, Neeraj Vij, Steven Mazur |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cystic Fibrosis SAHA (suberoylanilide hydroxamic acid) Cystic Fibrosis Transmembrane Conductance Regulator Inflammation Adaptive Immunity Hydroxamic Acids Cystic fibrosis Pathogenesis 03 medical and health sciences Mice HDAC medicine Animals Humans CFTR Lung lcsh:RC705-779 Mice Knockout biology Chemistry Research FOXP3 lcsh:Diseases of the respiratory system respiratory system medicine.disease Cystic fibrosis transmembrane conductance regulator Immunity Innate 3. Good health Histone Deacetylase Inhibitors Mice Inbred C57BL 030104 developmental biology HEK293 Cells Myeloperoxidase Cancer research biology.protein Tumor necrosis factor alpha Histone deacetylase activity medicine.symptom Inflammation Mediators |
| Zdroj: | Respiratory Research Respiratory Research, Vol 19, Iss 1, Pp 1-12 (2018) |
| ISSN: | 1465-993X |
| Popis: | Background Chronic lung disease resulting from dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and NFκB-mediated neutrophilic-inflammation forms the basis of CF-related mortality. Here we aimed to evaluate if HDAC inhibition controls Pseudomonas-aeruginosa-lipopolysaccharide (Pa-LPS) induced airway inflammation and CF-lung disease. Methods For in vitro experiments, HEK293-cells were transfected with IL-8 or NFκB-firefly luciferase, and SV40-renilla- luciferase reporter constructs or ΔF508-CFTR-pCEP, followed by treatment with suberoylanilide hydroxamic acid (SAHA), Trichostatin-A (TSA) and/or TNFα. For murine studies, Cftr+/+ or Cftr−/− mice (n = 3) were injected/instilled with Pa-LPS and/or treated with SAHA or vehicle control. The progression of lung disease was monitored by quantifying changes in inflammatory markers (NFκB), cytokines (IL-6/IL-10), neutrophil activity (MPO, myeloperoxidase and/or NIMP-R14) and T-reg numbers. Results SAHA treatment significantly (p |
| Databáze: | OpenAIRE |
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