Affiliation:
1. Medical College of Soochow University
2. Anhui Medical University
Abstract
Abstract
Backgrounds:
IL-33 is an important pro-inflammatory factor involved in the schistosomiasis liver fibrosis. The inducible costimulator (ICOS) could bind to ICOS ligand (ICOSL), participating in chronic schistosomiasis.
Methods
The levels of IL-33 were determined in ICOSL-KO and WT mice infected with Schistosoma japonicum (S. japonicum), respectively. Then recombinant IL-33 (rIL-33) was injected into ICOSL-KO mice infected with S. japonicum.
Results
The concentrations of IL-33 were lower in ICOSL-KO mice that in WT mice. Furthermore, the injection of rIL-33 successfully aggravated liver fibrosis in ICOSL-KO mice, increased the numbers of lymphocyte antigen 6C (Ly6C)hi, enhanced the expression of C-C chemokine ligand (CCL)2, CCL5 and C-X-C motif chemokine 2 (CXCL2), and promoted polarization of T helper (Th) cells to Th2 cells, as well as induced the autophagy and apoptosis of hepatic stellate cells (HSCs).
Conclusions
Overall, the liver fibrosis was aggravated in ICOSL-KO mice along with the rIL-33, which could skew the polarization of Mφ, induce Th cells activation, HSCs apoptosis and autophagy through Smad2/3 and TGF-β signaling pathway. Our study gives an insight into antagonizing IL-33 as a potential target against liver fibrosis in ICOSL-KO mice.
Publisher
Research Square Platform LLC