Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and f... more Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC). βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.
The inflammatory cytokine TNF-α is a central mediator in many immune-mediated diseases,
such as C... more The inflammatory cytokine TNF-α is a central mediator in many immune-mediated diseases, such as Crohn’s disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNFΔARE mice; in which a systemic TNF-α overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNFΔARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNFΔARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNFΔARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNFΔARE mice. The lung responses towards CS in TNFΔARE mice however depend on the duration of CS exposure.
Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and f... more Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC). βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.
The inflammatory cytokine TNF-α is a central mediator in many immune-mediated diseases,
such as C... more The inflammatory cytokine TNF-α is a central mediator in many immune-mediated diseases, such as Crohn’s disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNFΔARE mice; in which a systemic TNF-α overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNFΔARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNFΔARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNFΔARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNFΔARE mice. The lung responses towards CS in TNFΔARE mice however depend on the duration of CS exposure.
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such as Crohn’s disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary
disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is
a prominent common risk factor in these TNF-dependent diseases. We exposed TNFΔARE
mice; in which a systemic TNF-α overexpression leads to the development of inflammation;
to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on
CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression
of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs
of TNFΔARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure,
this aggravation was no longer observed. TNFΔARE mice have no increases in CD4+ and
CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure.
In the gut and joints of TNFΔARE mice, 2 or 4 weeks of CS exposure did not modulate
the development of inflammation. In conclusion, CS exposure does not modulate gut and
joint inflammation in TNFΔARE mice. The lung responses towards CS in TNFΔARE mice however
depend on the duration of CS exposure.
such as Crohn’s disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary
disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is
a prominent common risk factor in these TNF-dependent diseases. We exposed TNFΔARE
mice; in which a systemic TNF-α overexpression leads to the development of inflammation;
to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on
CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression
of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs
of TNFΔARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure,
this aggravation was no longer observed. TNFΔARE mice have no increases in CD4+ and
CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure.
In the gut and joints of TNFΔARE mice, 2 or 4 weeks of CS exposure did not modulate
the development of inflammation. In conclusion, CS exposure does not modulate gut and
joint inflammation in TNFΔARE mice. The lung responses towards CS in TNFΔARE mice however
depend on the duration of CS exposure.