Leptin and leptin receptor expression in asthma

Background

The adipokine leptin is a potential new mediator for bronchial epithelial homeostasis. Asthma is a chronic inflammatory disease characterized by airway remodeling that might affect disease chronicity and severity. TGF-β is a tissue growth factor the dysregulation of which is associated with airway remodeling.

Objective

We sought to determine whether a bronchial epithelial dysfunction of the leptin/leptin receptor pathway contributes to asthma pathogenesis and severity.

Methods

We investigated in vitro the presence of leptin/leptin receptor on human bronchial epithelial cells. Then we studied the effect of TGF-β and fluticasone propionate on leptin receptor expression. Finally, the role of leptin on TGF-β release and cell proliferation was analyzed. Ex vivo we investigated the presence of leptin/leptin receptor in the epithelium of bronchial biopsy specimens from subjects with asthma of various severities and from healthy volunteers, and some features of airway remodeling, such as reticular basement membrane (RBM) thickness and TGF-β expression in the epithelium, were assessed.

Results

In vitro bronchial epithelial cells express leptin/leptin receptor. TGF-β decreased and fluticasone propionate increased leptin receptor expression, and leptin decreased the spontaneous release of TGF-β and increased cell proliferation. Ex vivo the bronchial epithelium of subjects with mild, uncontrolled, untreated asthma showed a decrease expression of leptin and its receptor and an increased RBM thickness and TGF-β expression when compared with values seen in healthy volunteers. Furthermore, severe asthma was associated with a reduced expression of leptin and its receptor and an increased RBM thickness with unaltered TGF-β expression.

Conclusions

Decreased expression of leptin/leptin receptor characterizes severe asthma and is associated with airway remodeling features.

Key words: Leptin, leptin receptor, severe asthma, epithelium, TGF-β, remodeling

Abbreviations used: BECs, Bronchial epithelial cells from brushings, FP, Fluticasone propionate, C, Healthy control volunteer, ICS, Subject with mild asthma controlled with inhaled corticosteroids, NHBE, Normal human bronchial epithelial, RBM, Reticular basement membrane, SDA, Subject with severe uncontrolled asthma treated with inhaled and oral corticosteroids, UA, Subject with mild uncontrolled untreated asthma