[HTML][HTML] Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice

X Su, MR Looney, H Su, JW Lee, Y Song… - Inflammation …, 2011 - Springer
X Su, MR Looney, H Su, JW Lee, Y Song, MA Matthay
Inflammation research, 2011Springer
Objective and design Cystic fibrosis transmembrane conductance regulator (CFTR)
regulates infection and inflammation. In this study, we investigated whether a lack of
functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung
inflammation and injury. Materials and methods CFTR-inhibited or F508del-CFTR-mutated
neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and
NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone …
Objective and design
Cystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury.
Materials and methods
CFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response.
Results
Pharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution.
Conclusions
Lack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury.
Springer