| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T241 |
0-146 |
Sentence |
denotes |
The lack of functional CFTR in macrophages results in an increased production of inflammatory cytokines, and impaired pathogen clearance capacity. |
| T242 |
147-352 |
Sentence |
denotes |
The diminished expression of HLA-DQ and HLA-DR (MHC-II molecules) on monocytes derived from ΔF508-CFTR homozygous CF subjects [166], might explain the impaired pathogen clearance ability of CF macrophages. |
| T243 |
353-494 |
Sentence |
denotes |
In addition, CFTR deficiency has been implicated in diminished Treg effector function and a more pronounced Th2-biased immune response [167]. |
| T244 |
495-653 |
Sentence |
denotes |
The CF defect has also been shown to affect the activation of neutrophils [168], which are the cells responsible for the first line of defense in the airways. |
| T245 |
654-1048 |
Sentence |
denotes |
Although, airway epithelial cells and lung-resident macrophages sense the invading pathogens and secrete a plethora of factors to induce the recruitment and activation of neutrophils, neutrophils from CF subjects have diminished phagocytic potentials by virtue of the reduced cell surface expression of toll-like receptors (TLRs) and disrupted chloride transport to the phagolysosome [169,170]. |
| T246 |
1049-1122 |
Sentence |
denotes |
Thus the CFTR mutation in CF results in impaired bacterial killing [171]. |
| T247 |
1123-1270 |
Sentence |
denotes |
Moreover, CF neutrophils also demonstrate an increased capacity to release their primary granule contents such as MPO and neutrophil elastase (NE). |
| T248 |
1271-1370 |
Sentence |
denotes |
The uncontrolled release of these enzymes causes lung tissue damage and severe airway inflammation. |
| T249 |
1371-1700 |
Sentence |
denotes |
We have shown that P. aeruginosa LPS-induced MPO levels can be reduced by treatment with the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), plausibly by restoring the trafficking of ΔF508-CFTR, suggesting that a functional CFTR is required to keep a tab on uncontrolled neutrophil activation [172]. |
| T250 |
1701-1906 |
Sentence |
denotes |
Mechanistically, an absence or dysfunction of CFTR in neutrophils results in the deactivation of the guanosine triphosphate (GTP)-binding protein Rab27a, which causes impaired granule exocytosis [168,172]. |
| T251 |
1907-2136 |
Sentence |
denotes |
Several studies now agree that the pharmacological inhibition of CFTR or the mutant ΔF508-CFTR is sufficient to cause deregulated neutrophil activation via the activation of the NFκB pathway, resulting in hyperinflammation [172]. |
