Leptin and leptin receptor expression in asthma - 20/08/11
, Elisabetta Pace, MD a, Pascal Chanez, MD b, Delphine Gras, PhD b, Isabelle Vachier, PhD c, Giuseppina Chiappara, PhD a, Maurizio La Guardia, MD d, Stefania Gerbino, PhD a, d, Mirella Profita, PhD a, Mark Gjomarkaj, MD a
Reprint requests: Andreina Bruno, PhD, Istituto di Biomedicina e Immunologia Molecolare (IBIM), Consiglio Nazionale delle Ricerche (CNR), Via Ugo La Malfa, 153, 90146 Palermo, Italy.Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Leptin, leptin receptor, severe asthma, epithelium, TGF-β, remodeling
Abbreviations used : BECs, FP, C, ICS, NHBE, RBM, SDA, UA
Plan
| Supported by INSERM-CNR contract. |
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| Disclosure of potential conflict of interest: P. Chanez has received research support from Schering-Plough and has served as an advisor for all of the respiratory drug companies. The rest of the authors have declared that they have no conflict of interest. |
Vol 124 - N° 2
P. 230 - août 2009 Retour au numéro
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