Background: The adipokine leptin is a potential new mediatorfor bronchial epithelial homeostasis. Asthma is a chronicinflammatory disease characterized by airway remodeling thatmight affect disease chronicity and severity. TGF-b is a tissuegrowth factor the dysregulation of which is associated withairway remodeling.Objective: We sought to determine whether a bronchialepithelial dysfunction of the leptin/leptin receptor pathwaycontributes to asthma pathogenesis and severity.Methods: We investigated in vitro the presence of leptin/leptinreceptor on human bronchial epithelial cells. Then we studiedthe effect of TGF-b and fluticasone propionate on leptinreceptor expression. Finally, the role of leptin on TGF-b releaseand cell proliferation was analyzed. Ex vivo we investigated thepresence of leptin/leptin receptor in the epithelium of bronchialbiopsy specimens from subjects with asthma of variousseverities and from healthy volunteers, and some features ofairway remodeling, such as reticular basement membrane(RBM) thickness and TGF-b expression in the epithelium, wereassessed.Results: In vitro bronchial epithelial cells express leptin/leptinreceptor. TGF-b decreased and fluticasone propionate increasedleptin receptor expression, and leptin decreased the spontaneousrelease of TGF-b and increased cell proliferation. Ex vivo thebronchial epithelium of subjects with mild, uncontrolled,untreated asthma showed a decrease expression of leptin and itsreceptor and an increased RBM thickness and TGF-bexpression when compared with values seen in healthyvolunteers. Furthermore, severe asthma was associated with areduced expression of leptin and its receptor and an increasedRBM thickness with unaltered TGF-b expression.Conclusions: Decreased expression of leptin/leptin receptorcharacterizes severe asthma and is associated with airwayremodeling features.
|Numero di pagine||8|
|Rivista||Journal of Allergy and Clinical Immunology|
|Stato di pubblicazione||Published - 2009|
All Science Journal Classification (ASJC) codes
- Immunology and Allergy