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 level... More
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.
