Stem cell factor in nasal polyposis and allergic rhinitis: increased expression by structural cells is suppressed by in vivo topical corticosteroids.
BACKGROUND
Mast cells are increased in nasal polyp (Np) and allergic rhinitis (AR) tissue and are suppressed by topical corticosteroid treatment. Stem cell factor (SCF), a mast cell growth and survival factor, may explain these phenomena.


OBJECTIVE
We investigated structural cell gene expression and production of SCF in nasal tissues in patients who had received and who had not received in vivo intranasal corticosteroid therapy.


METHODS
Northern blot analyses for messenger RNA and ELISA for biologically active SCF protein from cultured Np epithelial cells and fibroblasts were performed. Immunostaining for SCF in cultured and tissue nasal structural cells in the presence or absence of steroid treatment was also performed.


RESULTS
We detected significant expression of SCF mRNA and protein by cultured Np epithelial cells and Np fibroblasts; Np fibroblast SCF supported the differentiation of mast cells in vitro. There were more immunoreactive SCF-positive Np epithelial cells in patients with AR than in control subjects (97.2 +/- 2.8 vs 45.6 +/- 22.0%; p < 0.0001). SCF that could be immunostained was significantly diminished overall in Np structural cells in the group given in vivo steroid treatment, with a modest (trend to significant) effect on any given cell type analyzed. In vitro treatment with budesonide of SCF-producing fibroblasts demonstrated inhibition of unstimulated, primary Np fibroblasts but not of IL-1-stimulated fibroblasts or transformed cell lines.


CONCLUSIONS
Human Np and AR tissue structural cells express and produce increased SCF. Our in vitro studies suggest that intranasal steroids blunt SCF expression in Nps, an effect that may be responsible for a decrease in mast cells and symptoms.
Kim
Y K
YK
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Nakagawa
N
N
Nakano
K
K
Sulakvelidze
I
I
Dolovich
J
J
Denburg
J
J
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015152:Blotting, Northern; D019819:Budesonide; D002478:Cells, Cultured; D053818:Chymases; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D009298:Nasal Polyps / Q000188:drug therapy* / Q000276:immunology; D011282:Pregnenediones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D019089:Stem Cell Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053802:Tryptases
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D007375:Interleukin-1; D011282:Pregnenediones; D012333:RNA, Messenger; D019089:Stem Cell Factor; D019819:Budesonide; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases