Schistosoma japonicum soluble egg antigen inhibits TNF-α-induced IL-34 expression in hepatic stellate cells

Hepatic fibrosis is characterized by the activation of the main collagen-producing cells of the liver, hepatic stellate cells, and is associated with inflammation. Although the involvement of numerous inflammatory cytokines has been reported, IL-34 in particular has recently been identified as a profibrotic factor in the development of hepatic fibrosis. Previous studies have found that schistosome eggs can lead to transcriptional downregulation of fibrosis-associated genes, and based on this evidence, we attempted to investigate whether or not IL-34 is regulated by soluble egg antigen (SEA). Our findings testified that SEA inhibited TNF-α-induced expression of IL-34 at both the mRNA and protein levels. Furthermore, results from reporter assays and qPCR experiments demonstrated that SEA impaired the activation of NF-κB triggered by TNF-α, as well as the transcription of downstream genes. More importantly, SEA decreased the phosphorylation and degradation of IκBα induced by TNF-α, two events that are hallmarks of canonical NF-κB activation. In conclusion, our results suggest that, in hepatic stellate cells, SEA impairs NF-κB activation and thereby inhibits TNF-α-induced IL-34 expression. These findings reveal a previously unidentified target and signaling pathway that support SEA’s involvement in hepatic fibrosis and provide a new clue to guide ongoing research into the anti-fibrotic effects of SEA.