Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica

Background: Hepatic granuloma formation and fibrosis as the consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology ofSchistosoma japonicuminfection. It has been proposed that fucoidan, a sulfated polysaccharide existing naturally in brown seaweedFucus vesiculosus, plays a diversified role to perform immunomodulatory activities. However, whether fucoidan functions in the host hepatic pathology is unknown and identifying the potential mechanism that is responsible for hepatic improvement is still necessary. Methods: We evaluated the hepatic pathology fromS. japonicum-infected mice after treatment with fucoidan. qRT-PCR and immunofluorescence were used to detect the pro- or anti-inflammatory factors and the phosphorylated p65 in the livers. In addition, flow cytometry was also performed to investigate the T cell subsets in theS. japonicum-infected mice after treatment with fucoidan, and functional molecules relatively specific to Treg cells were detectedin vitro. Furthermore, macrophages were treated with fucoidanin vitroand to detect the inflammatory cytokines. Results: Treatment with fucoidan significantly reduced the hepatic granuloma size and fibrosis response duringS. japonicuminfection. The attenuated phospho-p65 protein levels and the mRNA levels of pro-inflammatory cytokines (IL-6, IL-12 and TNF-alpha) were observed in the livers from fucoidan-treatedS. japonicum-infected mice; however, the mRNA levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased. In addition, the infiltration of Treg cells was significantly enhanced both in the livers and spleens from fucoidan-treatedS. japonicum-infected mice. Consistent with this, the mRNA levels of IL-10 and TGF-beta were dramatically increased in the livers fromS. japonicum-infected mice after fucoidan treatment. Furthermore,in vitrostimulated splenocytes with fucoidan resulted in increasing Treg cells in splenocytes as well as the functional expression of CC chemokine receptor type 4 (CCR4) and CXC chemokine receptor type 5 (CXCR5) in Treg cells. Additionally, fucoidan promoted the mRNA levels of IL-4 and IL-13 in macrophages. Conclusions: These findings suggest an important role of natural fucoidan in reducing hepatic pathology in the progress ofS. japonicuminfection with a stronger Treg response, which may reveal a new potential therapeutic strategy for hepatic disease caused by parasitic chronic infection.