IRF3 is an Important Molecule in the UII/UT System and Mediates Immune Inflammatory Injury in Acute Liver Failure

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jul 25

PMID 27448985

Citations 6

Authors

Liang-Ming Liu

Wen-Juan Tu

Tong Zhu

Xiao-Ting Wang

Zhi-Li Tan

Huan Zhong

De-Yong Gao

Dong-Yu Liang

Affiliations

Soon will be listed here.

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.

Citing Articles

To re-examine the intersection of microglial activation and neuroinflammation in neurodegenerative diseases from the perspective of pyroptosis.

Li Y, Li Y, Zhu Z Front Aging Neurosci. 2023; 15:1284214.

PMID: 38020781 PMC: 10665880. DOI: 10.3389/fnagi.2023.1284214.

The network map of urotensin-II mediated signaling pathway in physiological and pathological conditions.

Rex D, Suchitha G, Palollathil A, Kanichery A, Keshava Prasad T, Dagamajalu S J Cell Commun Signal. 2022; 16(4):601-608.

PMID: 35174439 PMC: 9733756. DOI: 10.1007/s12079-022-00672-4.

IRF3-mediated pathogenicity in a murine model of human hepatitis A.

Sun L, Li Y, Misumi I, Gonzalez-Lopez O, Hensley L, Cullen J PLoS Pathog. 2021; 17(9):e1009960.

PMID: 34591933 PMC: 8509855. DOI: 10.1371/journal.ppat.1009960.

Urantide prevents CCl4‑induced acute liver injury in rats by regulating the MAPK signalling pathway.

Li Y, Guo Z, Cui H, Wang T, Xu Y, Zhao J Mol Med Rep. 2021; 24(4).

PMID: 34328202 PMC: 8365596. DOI: 10.3892/mmr.2021.12329.

Low type I interferon response in COVID-19 patients: Interferon response may be a potential treatment for COVID-19.

Salman A, Waheed M, Ali-Abdulsahib A, Atwan Z Biomed Rep. 2021; 14(5):43.

PMID: 33786172 PMC: 7995242. DOI: 10.3892/br.2021.1419.

References

Rustagi A, Gale Jr M . Innate antiviral immune signaling, viral evasion and modulation by HIV-1. J Mol Biol. 2013; 426(6):1161-77. PMC: 7425209. DOI: 10.1016/j.jmb.2013.12.003. View

Cirillo P, De Rosa S, Pacileo M, Gargiulo A, Angri V, Fiorentino I . Human urotensin II induces tissue factor and cellular adhesion molecules expression in human coronary endothelial cells: an emerging role for urotensin II in cardiovascular disease. J Thromb Haemost. 2008; 6(5):726-36. DOI: 10.1111/j.1538-7836.2008.02923.x. View

Segain J, Rolli-Derkinderen M, Gervois N, Raingeard de la Bletiere D, Loirand G, Pacaud P . Urotensin II is a new chemotactic factor for UT receptor-expressing monocytes. J Immunol. 2007; 179(2):901-9. DOI: 10.4049/jimmunol.179.2.901. View

Coulouarn Y, Lihrmann I, Jegou S, Anouar Y, Tostivint H, Beauvillain J . Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord. Proc Natl Acad Sci U S A. 1998; 95(26):15803-8. PMC: 28125. DOI: 10.1073/pnas.95.26.15803. View

Jiang X, Li Z, Jiang S, Tong X, Zou X, Wang W . Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-κB pathway. Int J Mol Med. 2016; 37(3):773-80. DOI: 10.3892/ijmm.2016.2483. View

Thomas E, Gonzalez V, Li Q, Modi A, Chen W, Noureddin M . HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons. Gastroenterology. 2012; 142(4):978-88. PMC: 3435150. DOI: 10.1053/j.gastro.2011.12.055. View

Leifeld L, Clemens C, Heller J, Trebicka J, Sauerbruch T, Spengler U . Expression of urotensin II and its receptor in human liver cirrhosis and fulminant hepatic failure. Dig Dis Sci. 2009; 55(5):1458-64. DOI: 10.1007/s10620-009-0875-4. View

Vaudry H, Do Rego J, Le Mevel J, Chatenet D, Tostivint H, Fournier A . Urotensin II, from fish to human. Ann N Y Acad Sci. 2010; 1200:53-66. DOI: 10.1111/j.1749-6632.2010.05514.x. View

Douglas S, Tayara L, Ohlstein E, Halawa N, Giaid A . Congestive heart failure and expression of myocardial urotensin II. Lancet. 2002; 359(9322):1990-7. DOI: 10.1016/S0140-6736(02)08831-1. View

10.

Karaghiosoff M, Steinborn R, Kovarik P, Kriegshauser G, Baccarini M, Donabauer B . Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat Immunol. 2003; 4(5):471-7. DOI: 10.1038/ni910. View

11.

Siegfried A, Berchtold S, Manncke B, Deuschle E, Reber J, Ott T . IFIT2 is an effector protein of type I IFN-mediated amplification of lipopolysaccharide (LPS)-induced TNF-α secretion and LPS-induced endotoxin shock. J Immunol. 2013; 191(7):3913-21. DOI: 10.4049/jimmunol.1203305. View

12.

Liehl P, Zuzarte-Luis V, Chan J, Zillinger T, Baptista F, Carapau D . Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection. Nat Med. 2013; 20(1):47-53. PMC: 4096771. DOI: 10.1038/nm.3424. View

13.

Liu L, Liang D, Ye C, Tu W, Zhu T . The UII/UT system mediates upregulation of proinflammatory cytokines through p38 MAPK and NF-κB pathways in LPS-stimulated Kupffer cells. PLoS One. 2015; 10(3):e0121383. PMC: 4372515. DOI: 10.1371/journal.pone.0121383. View

14.

Desai N, Sajjad J, Frishman W . Urotensin II: a new pharmacologic target in the treatment of cardiovascular disease. Cardiol Rev. 2008; 16(3):142-53. DOI: 10.1097/CRD.0b013e31815c8048. View

15.

Liu S, Cai X, Wu J, Cong Q, Chen X, Li T . Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015; 347(6227):aaa2630. DOI: 10.1126/science.aaa2630. View

16.

Tarassishin L, Bauman A, Suh H, Lee S . Anti-viral and anti-inflammatory mechanisms of the innate immune transcription factor interferon regulatory factor 3: relevance to human CNS diseases. J Neuroimmune Pharmacol. 2012; 8(1):132-44. DOI: 10.1007/s11481-012-9360-5. View

17.

Maguire J, Kuc R, Wiley K, Kleinz M, Davenport A . Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries. Peptides. 2004; 25(10):1767-74. DOI: 10.1016/j.peptides.2004.01.028. View

18.

Liu L, Zhao L, Liang D, Yu F, Ye C, Tu W . Effects of urotensin-II on cytokines in early acute liver failure in mice. World J Gastroenterol. 2015; 21(11):3239-44. PMC: 4363753. DOI: 10.3748/wjg.v21.i11.3239. View

19.

Liu D, Chen J, Wang J, Zhang Z, Ma X, Jia J . Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension. Int J Mol Med. 2010; 25(6):845-51. DOI: 10.3892/ijmm_00000413. View

20.

Liang D, Liu L, Ye C, Zhao L, Yu F, Gao D . Inhibition of UII/UTR system relieves acute inflammation of liver through preventing activation of NF-κB pathway in ALF mice. PLoS One. 2013; 8(6):e64895. PMC: 3670940. DOI: 10.1371/journal.pone.0064895. View