Michio Kuramochi

Attenuation of allergic inflammation by neutralization of IGF-I in murine asthmatic models

092 Attenuation of Allergic Inflammation by Neutralization of IGF-I in Murine Asthmatic Models N. Yamashita j, H. Tashimo 1, M. Nakajima I , H. Ishida I, M. KuramochP, E Kaneko 1, R. KawashimaJ, T. Horiuchi 2, K. Ohtal; ITeikyo University School of Medicine, Tokyo, JAPAN, 2Kanto Central Hospital, Tokyo, JAPAN. RATIONALE: It has been suggested that airway wall thickening in asthma involves the production of extracellular matrix (ECM) components, including collagen, by myofibroblasts. In this study, we tried to clarify the role of IGF-I, a progression factor of fibroblast, in asthma. METHODS: Mice were immunized with ovalubmin + alum and challenged with ovalbumin inhalation, Anti-lGF-I neutralizing antibody was continuously introduced using osmotic pump during challenge. Pulmonary function was analyzed using whole body plethysmography before and after achetylcholine inhalation. RESULTS: Anti-IGF-I neutralizing antibody significantly inhibited the elevation of airway resistance and the increase of the airway wall thickening induced with OA inhalation. Airway inflammation was also inhibited by IGF-! neutralizing antibody, confirming by BALF cell analysis and histological examination, cDNA array analysis revealed that the neutralization of IGF-1 induced the activation of caspase1 and the reduction of anti-apoptotic Bag1 mRNA. CONCLUSIONS: In conclusion, not only induction of fibroblast proliferation but also anti-apoptotic effects of IGF-I may play a role in the process of airway inflammation and remodeling of asthma. Funding: Se!f-funded