Nitric oxide and collagen expression in allergic upper-airway disease.
BACKGROUND
The presence of nitric oxide (NO) in high concentrations has been described in the nasal mucosa of patients with untreated allergic rhinitis. We sought to examine the role of exogenous, as well as endogenous, NO in the production of collagen type I and type III by human nasal fibroblasts.


METHODS
Primary cultured fibroblasts derived from eosinophilic nasal polyps were exposed to NO donors (500 microM of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) 1000 micoM of 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (DETA-NONOate)) and various other compounds over a 24-hour incubation period. Collagen production was evaluated qualitatively by immunocytochemistry and quantitatively by Western blot analysis.


RESULTS
Maximally stimulated fibroblasts established a 2,2-fold increase in the production of type III collagen relative type 1, as compared with baseline. Oxyhemoglobin, an NO scavenger, abolished this effect. SNAP (500 microM) caused a 15.68 +/- 0.68% increase in collagen type I synthesis as compared with unstimulated controls (p < 0.05). In contrast, incubation with SNAP caused an increase in collagen type III production by a factor of 34.68 +/- 0.32% (p < 0.05).


CONCLUSIONS
NO stimulates collagen expression in human nasal polyp-derived fibroblasts. This stimulation appeared to favor the up-regulation of collagen type III, leading to a shift in the ratio of collagen type I to type III production.
Department of Otolaryngology, Sir Mortimer B. Davis Jewish General Hospital, and Meakins-Christie Laboratories, Respiratory Division, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Marc A
MA
Tewfik
Julio F
JF
Bernardes
Jichuan
J
Shan
Michelle
M
Robinson
Saul
S
Frenkiel
David H
DH
Eidelman
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D017364:Collagenases / Q000032:analysis / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology; D009298:Nasal Polyps / Q000150:complications / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D003094:Collagen; D017364:Collagenases; D010396:Penicillamine