TY - JOUR T1 - 3-(2,4-Dichlorophenyl)-4-(1-methyl-1<em>H</em>-indol-3-yl)-1<em>H</em>-pyrrole-2,5-dione (SB216763), a Glycogen Synthase Kinase-3 Inhibitor, Displays Therapeutic Properties in a Mouse Model of Pulmonary Inflammation and Fibrosis JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 785 LP - 794 DO - 10.1124/jpet.109.153049 VL - 332 IS - 3 AU - Carmela Gurrieri AU - Francesco Piazza AU - Marianna Gnoato AU - Barbara Montini AU - Lucia Biasutto AU - Cristina Gattazzo AU - Enrico Brunetta AU - Anna Cabrelle AU - Francesco Cinetto AU - Raffaele Niero AU - Monica Facco AU - Spiridione Garbisa AU - Fiorella Calabrese AU - Gianpietro Semenzato AU - Carlo Agostini Y1 - 2010/03/01 UR - http://jpet.aspetjournals.org/content/332/3/785.abstract N2 - Glycogen synthase kinase (GSK)-3 modulates the production of inflammatory cytokines. Because bleomycin (BLM) causes lung injury, which is characterized by an inflammatory response followed by a fibrotic degeneration, we postulated that blocking GSK-3 activity with a specific inhibitor could affect the inflammatory and profibrotic cytokine network generated in the BLM-induced process of pulmonary inflammation and fibrosis. Thus, here we investigated the effects of the GSK-3 inhibitor 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763) on a BLM-induced lung fibrosis model in mice. SB216763 prevented lung inflammation and the subsequent fibrosis when coadministered with BLM. Bronchoalveolar lavage fluid analysis of mice treated with BLM plus SB216763 revealed a significant reduction in BLM-induced alveolitis. Furthermore, SB216763 treatment was associated with a significantly lower production of inflammatory cytokines by macrophages. BLM-treated mice that received SB216763 developed alveolar epithelial cell damage and pulmonary fibrosis to a significantly lower extent compared with BLM-treated controls. These findings suggest that GSK-3 inhibition has a protective effect on lung fibrosis induced by BLM and candidate GSK-3 as a potential therapeutic target for preventing pulmonary fibrosis.Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics ER -