Hepatic progenitor cells promote the repair of schistosomiasis liver injury by inhibiting IL-33 secretion in mice

Abstract

Background Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown. Methods In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33−/− mice infected with S. japonicum. Results We found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs’ expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33−/− mice with HPCs’ expansion. However, liver injury was more attenuated in IL-33−/− mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK. Conclusions Our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

Interleukin-33 deficiency prevents biliary injuries and repairments caused by Clonorchis sinensis via restraining type 2 cytokines

“…To investigate the role and mechanisms of IL-33 in type 2 immune response during biliary injuries caused by C. sinensis infection, we first generated IL-33 KO mice with the same genetic background (BALB/c) using CRISPR-Cas9 gene-editing systems [ 10 ]. Then, we established a biliary injury mouse model by infection with C. sinensis for 8 weeks.…”

“…Wild-type mice and IL-33 KO mice (BALB/c female, 6–8 weeks, weight 18–20 g) were used for the study. Wild-type mice were purchased from the Beijing Vital River Laboratory Animal Technology Co., Ltd. IL-33 KO mice were generated using CRISPR/Cas9 technology as previously published [ 10 ]. All the mice were bred and housed under specific pathogen-free conditions maintained at 23 °C ± 2 °C with 12 h light/12 h dark cycles at the animal center of Xuzhou Medical University.…”

Design, Synthesis, and Antiproliferative Activities of 1,3‐Disubstituted 2‐Thioxoimidazolidin‐4‐one Derivatives against HepG2 and MCF‐7 Cells

“…β-actin serves as a cytoskeleton protein to produce filaments. [49] Compound 11's potential capacity to inhibit β-catenin expression may underlie its anti-inflammatory effects in the present investigation. Our results demonstrated that compound 11 reduced β-catenin expression in HepG2 by 0.284 fold, compared to control HepG2 cells (0.517 fold) (Figure 8).…”

Pathology and molecular mechanisms of Schistosoma japonicum-associated liver fibrosis

“…IL-33 is a part of the IL-1 family and is normally present in the nucleus and released into the extracellular compartment in response to tissue damage ( Bai et al., 2021 ). IL-33 plays an important role in immunity to schistosome infection, and IL-33 levels are positively correlated with the progression of egg granuloma and liver fibrosis ( Zhang et al., 2021 ). IL-33 induces macrophage M2-type polarization and releases IL-5 and IL-13 to promote liver fibrosis ( Li et al., 2019 ).…”

“…IL-33 contributes to the maintenance of type II immune microenvironments in the liver of schistosome-infected mice. During chronic infections, Hepatic progenitor cells (HPCs) inhibit the secretion of IL-33 to promote tissue restoration and inhibit the development of liver fibrosis ( Zhang et al., 2021 ). Tissue Transglutaminase (tTG) regulates cell death and cytoskeletal rearrangement, however, tTG is also involved in the regulation of SSLF.…”