1. Inhibition of histone-deacetylase activity rescues inflammatory cystic fibrosis lung disease by modulating innate and adaptive immune responses
- Author
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Manish Bodas, Steven Mazur, Taehong Min, and Neeraj Vij
- Subjects
SAHA (suberoylanilide hydroxamic acid) ,Cystic fibrosis ,CFTR ,HDAC ,Lung ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract 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
- Published
- 2018
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