Research Papers: Immunology:
IRF3 is an important molecule in the UII/UT system and mediates immune inflammatory injury in acute liver failure
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Liang-ming Liu1, Wen-juan Tu1, Tong Zhu1, Xiao-ting Wang1, Zhi-li Tan1, Huan Zhong1, De-yong Gao1 and Dong-yu Liang1
1 Department of Hepatology, Songjiang Hospital Affiliated to the First People’s Hospital Shanghai Jiaotong University, Shanghai, China
Liang-ming Liu, email:
Keywords: IRF3; urotensin II; acute liver failure; immune-mediated inflammation; Kupffer cells; Immunology and Microbiology Section; Immune response; Immunity
Received: April 15, 2016 Accepted: June 07, 2016 Published: July 19, 2016
The urotensin II/urotensin receptor (UII/UT) system can mediate inflammatory liver injury in acute liver failure (ALF); however; the related mechanism is not clear. In this study, we confirmed that lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced up-regulation of liver interferon regulatory factor 3 (IRF3) in ALF mice, whereas the UT antagonist urantide inhibited the up-regulated liver IRF3. LPS stimulation induced IRF3 transcription and nuclear translocation and promoted the secretion of interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ in Kupffer cells (KCs); these effects in LPS-stimulated KCs were inhibited by urantide. Knockdown of IRF3 using an adenovirus expressing an IRF3 shRNA inhibited IFN-β transcription and secretion as well as tumor necrosis factor (TNF)-α and IL-1β secretion from LPS-stimulated KCs; additionally, IL-10 transcription and secretion were promoted in response to LPS. However, LPS-stimulated TNF-α and IL-1β mRNA was not affected in the KCs. The IRF3 shRNA also did not have a significant effect on the NF-κB p65 subunit and p38MAPK protein phosphorylation levels in the nuclei of LPS-stimulated KCs. Therefore, IRF3 expression and activation depended on the signal transduction of the UII/UT system, and played important roles in UII/UT-mediated immune inflammatory injury in the liver but did not affect NF-κB and p38 MAPK activity.
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