Role of insulin-like growth factor-I in allergen-induced airway inflammation and remodeling.
Insulin-like growth factor (IGF)-I is known to act on fibroblasts as a progression factor to push cells toward proliferation and activation to synthesize collagen. Subepithelial fibrosis, collagen deposition at the lamina reticularis, is part of the process of so-called remodeling and is a characteristic finding in the asthmatic airway. To study the role of IGF in the evolution of asthma, we used a model that involved immunization of mice with ovalbumin and alum, followed by an inhaled challenge of ovalbumin. IGF-I neutralizing antibody was continuously infused with an osmotic pump. Pulmonary function was analyzed using whole-body plethysmography before and after acetylcholine administration. It was found that OVA inhalation induced IGF-I expression at the site of the airway. IGF-I neutralizing Ab inhibited the elevation of airway resistance, airway inflammation, and an increase in airway wall thickening. The depression of ICAM-1 expression was accompanied by a diminution in airway inflammation. In conclusion, these results suggest that IGF-I is likely to be an important mediator of inflammation and remodeling in the asthmatic airway.
Yamashita
Naomi
N
Department of Pharmacology, Research Institute of Pharmaceutical Sciences, Musashino University, Japan.
Tashimo
Hiroyuki
H
Ishida
Hirofuni
H
Matsuo
Yukiko
Y
Arai
Hidenori
H
Nagase
Hiroyuki
H
Adachi
Tetsuya
T
Ohta
Ken
K
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D000485:Allergens; D000906:Antibodies; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D007334:Insulin-Like Growth Factor I; D010047:Ovalbumin