title: IRF3 is an important molecule in the UII/UT system and mediates immune inflammatory injury in acute liver failure.
abstract: 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.
authors.affiliation: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Liu
authors.affiliation: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Tu
authors.affiliation: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Wang
authors.affiliation: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Tan
authors.affiliation: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: De-Yong
authors.initials: DY
authors.lastname: Gao
authors.affiliation: Department of Hepatology, Songjiang Hospital Affiliated to the First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: Dong-Yu
authors.initials: DY
authors.lastname: Liang
mesh_terms: D021581:Active Transport, Cell Nucleus; D000256:Adenoviridae; D000818:Animals; D005688:Galactosamine / Q000378:metabolism; D007249:Inflammation; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism; D017114:Liver Failure, Acute / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014579:Urotensins / Q000737:chemistry / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D050838:Interferon Regulatory Factor-3; D015850:Interleukin-6; C494233:Irf3 protein, mouse; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C498144:Rela protein, mouse; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014579:Urotensins; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; C512325:urotensin II receptor, mouse; D005688:Galactosamine; D016899:Interferon-beta; D007371:Interferon-gamma; C029677:urotensin II; D048051:p38 Mitogen-Activated Protein Kinases
keywords: IRF3; Immune response; Immunity; Immunology and Microbiology Section; Kupffer cells; acute liver failure; immune-mediated inflammation; urotensin II