Effect of glucocorticoids on stem cell factor expression in human asthmatic bronchi.
BACKGROUND
Stem cell factor (SCF) is a major mast cell growth factor promoting differentiation, chemotaxis as well as inhibition of apoptosis of mast cells. Regulation of SCF expression by glucocorticoids has not yet been reported in human asthmatic bronchi.


OBJECTIVE
To evaluate SCF mRNA and protein expression in biopsy specimen and bronchoalveolar lavage fluid, respectively, and to determine the mast cell numbers in biopsy sections from control and asthmatic subjects treated or not with glucocorticoids.


METHODS
Volunteers were recruited out of pollen season. Asthmatic patients were allergic to common allergen extracts including grass and tree pollen, cat, dog or mite; three volunteers had non-allergic asthma. Mast cell numbers were counted after anti-human tryptase immunolabelling. SCF mRNA was quantified by real-time fluorescent PCR (LightCycler) after reverse transcription, and SCF protein was measured by ELISA.


RESULTS
Asthmatic patients not treated with glucocorticoids showed a 5.8-, 1.8- and 3.1-fold significant increase in SCF mRNA, protein levels and mast cell numbers, respectively, compared with healthy volunteers of the control group (7.8 and 1.3 pg/mug SCF mRNA/GAPDH; 99.8+/-11.5 and 56.0+/-11.0 pg/mL SCF protein; 103+/-21 and 33+/-8 mast cells/mm(2), respectively; P<0.05). In asthmatic patients treated with glucocorticoids, a significant decrease of SCF mRNA, protein levels and mast cell numbers was observed as compared with untreated asthmatic patients (1.1 pg/microg mRNA; 62.0+/-10.3 pg/mL SCF protein and 39+/-13 mast cells/mm(2); P<0.05), reaching levels comparable to those of the control group.


CONCLUSIONS
Our study shows that SCF is expressed in the bronchus in humans in vivo. This expression is increased in asthma, and is parallel to the increased mast cell numbers in the airways. Both increases were normalized in glucocorticoid-treated patients, strongly suggesting an involvement of SCF in the mast cell-associated asthmatic disease.
Da Silva
C A
CA
EA 3771, Faculté de Pharmacie, Université Louis Pasteur Strasbourg - I, Illkirch, Cedex, France.
Blay
F
F
Israel-Biet
D
D
Laval
A-M
AM
Glasser
N
N
Pauli
G
G
Frossard
N
N
D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*
D005938:Glucocorticoids; D012333:RNA, Messenger; D019089:Stem Cell Factor