Spermine Alleviates Acute Liver Injury by Inhibiting Liver-Resident Macrophage Pro-Inflammatory Response Through ATG5-Dependent Autophagy

Frontiers in Immunology
Shun ZhouLing Lu

Abstract

Liver-resident macrophages (Kupffer cells, KCs) and autophagy play critical roles in the pathogenesis of toxin-induced liver injury. Recent evidence indicates that autophagy can regulate macrophage M1/M2 polarization under different inflammatory conditions. Polyamines, including putrescine, spermidine, and spermine (SPM), are polycations with anti-oxidative, anti-aging, and cell autophagy induction properties. This study aimed to determine the mechanisms by which SPM protects against thioacetamide (TAA)-induced acute liver injury in a mouse model. Pretreatment with SPM significantly alleviated liver injury and reduced intrahepatic inflammation in TAA-induced liver injury compared to controls. SPM markedly inhibited M1 polarization, but promoted M2 polarization of KCs obtained from TAA-exposed livers, as evidenced by decreased IL-1β and iNOS gene induction but increased Arg-1 and Mrc-1 gene induction accompanied by decreased STAT1 activation and increased STAT6 activation. Furthermore, pretreatment with SPM enhanced autophagy, as revealed by increased LC3B-II levels, decreased p62 protein expression, and increased ATG5 protein expression in TAA-treated KCs. Knockdown of ATG5 in SPM-pretreated KCs by siRNA resulted in a significa...Continue Reading

References

Dec 2, 2000·Science·D J Klionsky, S D Emr
Apr 6, 2001·Cellular and Molecular Life Sciences : CMLS·T Thomas, T J Thomas
Mar 21, 2007·Biochemical Society Transactions·N BabbarR A Casero
Nov 27, 2007·International Journal of Cardiology·Salvatore PatanèRosario Evola
Jul 16, 2009·IUBMB Life·Anthony E Pegg
Dec 24, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bibo KeJerzy W Kupiec-Weglinski
Jan 30, 2010·Autophagy·Frank MadeoGuido Kroemer
Sep 22, 2010·Nature Immunology·Subhra K Biswas, Alberto Mantovani
Sep 29, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Raquel UrtasunNatalia Nieto
Oct 26, 2011·Nature Reviews. Immunology·Toby Lawrence, Gioacchino Natoli
Apr 10, 2012·Cell Metabolism·Subhra K Biswas, Alberto Mantovani
Apr 27, 2013·Nature·Thomas A WynnJeffrey W Pollard
Oct 8, 2013·The American Journal of Pathology·Hong-Min NiWen-Xing Ding
Nov 6, 2013·International Journal of Biological Macromolecules·Yong-Byung Chae, Moon-Moo Kim
Nov 28, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·Ahmad AmanzadaIhtzaz A Malik
Nov 28, 2013·Nature Communications·Vanessa BylesTiffany Horng
Dec 18, 2013·Immunology Letters·Pei-zhi LiKun He
Feb 2, 2016·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Can WeiChangqing Xu
Feb 26, 2016·Cellular & Molecular Immunology·Cynthia Ju, Frank Tacke
Apr 23, 2016·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Shinya OkumuraShinji Uemoto
Oct 12, 2016·Gastroenterology·Braedon McDonald, Paul Kubes
Jan 17, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jin-Kyu ParkYasuko Iwakiri
Jan 25, 2017·Autophagy·Tobias EisenbergFrank Madeo
Mar 8, 2017·Journal of Hepatology·Frank Tacke
Mar 21, 2017·Nature Reviews. Immunology·Oliver Krenkel, Frank Tacke
May 5, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Enpeng ZhaoMark J Czaja
May 19, 2017·Nature Communications·Yang HaiDavid W Christianson
Oct 13, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ling LuBibo Ke

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Citations

Feb 13, 2019·Cells·Young Jin JangSanguine Byun
Feb 14, 2019·Journal of Cellular and Molecular Medicine·Li ZhangZhigang Hu
Jul 12, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Song WeiLing Lu
Jan 22, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shihong WenWenqi Huang
Feb 14, 2020·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Leon A SokulskyPaul S Foster
Apr 16, 2020·Parasite Immunology·Gabriela Pessenda, João Santana da Silva
May 16, 2019·Neural Regeneration Research·Run-Hong TangHua-Yan Liu
Sep 24, 2019·World Journal of Gastroenterology : WJG·Han-Jing ZhangdiHai-Xing Jiang
Oct 13, 2018·International Journal of Molecular Sciences·Kuniyasu Soda
Apr 25, 2019·Amino Acids·Yvonne L LatourKeith T Wilson
Oct 9, 2020·Cell Proliferation·Yang OuyangShengrong Sun
Feb 16, 2021·World Journal of Hepatology·Elias KouroumalisDimitrios N Samonakis
Jan 21, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Steven A Bloomer, Eric D Moyer
May 16, 2021·Journal of Hematology & Oncology·Ziqi ZhangXiawei Wei

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Methods Mentioned

BETA
acetylation
light microscopy
PCR
ELISA

Software Mentioned

Stata

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