Targeting Insulin-Like Growth Factor-I in Allergen-Induced Airway Inflammation and Remodeling
Insulin-like growth factor-I (IGF-I) is known to act on fibroblasts as a progression factor to push the cells from G1 phase to mitosis in the cell cycle and activate them to synthesize collagen. Subepithelial fibrosis, i.e. 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 (OVA) 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 antibody inhibited the elevation of airway resistance, airway inflammation, and an increase in airway wall thickening. The depression of ICAM-1 and IGFBP 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.
KeywordsIdiopathic Pulmonary Fibrosis Airway Inflammation Allergy Clin Immunol Respir Crit Airway Hyperresponsiveness
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