Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression

Background: Tissue transglutaminase (tTG)-regulating IL-13 plays an important role in the pathogenesis of liver fibrosis resulting from Schistosoma japonicum (Sj) Infection. IL-33 and its receptor ST2 are involved in Th2-biased immune responses through the release of IL-5 and IL-13 and subsequent hepatic granuloma pathology induced by Sj Infection. However, the relationship between tTG, IL-33/ST2, and liver fibrosis during Schistosoma Infection has not been established.

Results: This study investigated the link between tTG and IL-33/ST2 in the induction of liver fibrogenesis during Sj Infection in mice. The extent of liver fibrosis coincided with an increase in tTG and IL-33/ST2 expression in the liver of infected mice between five to eight weeks, with a peak of correlation at six weeks after Sj Infection. The inhibition of tTG activity through cystamine administration or gene knockout alleviated the level of TLR4, NF-κB pathway molecules, IL-33/ST2, and the severity of liver fibrosis resulting from Sj Infection.

Conclusions: These results indicate that during Sj Infection tTG may control liver fibrosis at least partially through TLR4, NF-κB pathway activation and then IL-33/ST2. tTG, IL-33 or ST2 might be promising drug targets against liver fibrosis induced by Sj Infection.