Involvement of IL-13 and Tissue Transglutaminase in Liver Granuloma and Fibrosis afterSchistosoma japonicumInfection

Abstract

Schistosomiasis, one of the most devastating parasitic diseases, is caused bySchistosoma japonicum(Sj) infection resulting in serious liver fibrosis. Interleukin- (IL-) 13, which is produced byTH2  cells, is a critical profibrotic cytokine found in various organs, including the liver. Tissue transglutaminase (tTG), a group of multifunctional enzymes, serves a central function in the pathogenesis of chronic liver diseases. However, the relationship between IL-13, tTG, and liver fibrosis duringSchistosomainfection has not been established. This study investigated the involvement of IL-13 and tTG in liver fibrogenesis duringSjinfection in mice. Five weeks afterSjinfection, granuloma and fibrosis development in the liver coincided with an increase in IL-13 and tTG in the liver and the upregulation of serum IL-13 in infected mice. Administration of cystamine, an inhibitor of tTG, abrogated the increase in both tTG and IL-13 in infected mice and ameliorated liver fibrogenesis and granuloma development. This result establishes a novel link among IL-13, tTG, and liver granuloma and fibrosis underSjinfection. Based on their important functions in liver fibrosis induced bySjinfection, IL-13 and tTG could be promising potential drug targets against schistosomiasis.