Mo2003 Novel Guggulsterone Derivative GG-52 Inhibits NF-?B Signaling in Bone Marrow-Derived Dendritic Cells and Attenuates Colitis in IL-10 Deficient Mice

Abstract

G A A b st ra ct s The immunohistochemical studies of animals with colitis showed: i) a decrease in goblet cells of colonic mucosa (PAS reaction); ii) an increase in GSK-3 phosphorylation and of proteins phosphorylated in tyrosine residues (pY99). All these effects were reversed by the treatment with infliximab. By Western blot studies, we observed: i) an increase in the phosphorylation of IGF-1R, AKt, GSK-3 and mTor in the colon of animals with colitis. ii) an absence of stimulation of the phosphorylation of these components by IGF-I in animals with colitis. iii) a stimulation of the cascade GSK-3/β-catenin by IGF-I in control animals. iv) an abolition of the stimulatory effect of IGF-I on GSK-3/β-catenin during experimental colitis. Conclusions Taken together, our results suggest that during experimental colitis there is a state of resistance to IGF-I in the colon. This can be reversed by infliximab treatment. It has been shown that the mitogenic ability of IGF-I depends on the activation of the cascade GSK-3/β-catenin; therefore, our results point out the importance of the desensitization to IGF-I in the pathogenesis of IBD