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-beta 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-beta and fluticasone propionate on leptin receptor expression. Finally, the role of leptin on TGF-beta 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-beta expression in the epithelium, were assessed.


RESULTS
In vitro bronchial epithelial cells express leptin/leptin receptor. TGF-beta decreased and fluticasone propionate increased leptin receptor expression, and leptin decreased the spontaneous release of TGF-beta 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-beta 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-beta expression.


CONCLUSIONS
Decreased expression of leptin/leptin receptor characterizes severe asthma and is associated with airway remodeling features.
Bruno
Andreina
A
Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy. andreina@neomedia.it
Pace
Elisabetta
E
Chanez
Pascal
P
Gras
Delphine
D
Vachier
Isabelle
I
Chiappara
Giuseppina
G
La Guardia
Maurizio
M
Gerbino
Stefania
S
Profita
Mirella
M
Gjomarkaj
Mark
M
D000328:Adult; D000730:Androstadienes / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D000068298:Fluticasone; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020738:Leptin / Q000096:biosynthesis* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D054411:Receptors, Leptin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D007093:Imidazoles; D020738:Leptin; D009025:Morpholines; D011725:Pyridines; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000068298:Fluticasone; C093642:SB 203580