Schistosoma japonicum soluble egg antigen inhibits TNF-α-induced IL-34 expression in hepatic stellate cells
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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.
KeywordsHepatic fibrosis Hepatic stellate cell IL-34 NF-κB
We thank Dr. Hongbing Shu (Wuhan University) for providing the indicated plasmids.
This work was supported by the National Natural Science Foundation of China (81871677, 81471975), Jiangsu Planned Projects for Postdoctoral Research Funds (1701170B), and the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD).
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Conflict of interest
The authors declare that they have no conflict of interest.
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