Beyond Metabolism: Role of the Immune System in Hepatic Toxicity

被引:13
作者
Hastings, Kenneth L. [1 ]
Green, Martin D. [2 ]
Gao, Bin [3 ]
Ganey, Patricia E. [4 ]
Roth, Robert A. [4 ]
Burleson, Gary R. [5 ]
机构
[1] Hastings Toxicol Consulting LLC, Mt Airy, MD USA
[2] US FDA, Silver Spring, MD USA
[3] NIH, Lab Liver Dis, Bldg 10, Bethesda, MD 20892 USA
[4] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48824 USA
[5] BRT Burleson Res Technol Inc, Morrisville, NC 27560 USA
关键词
Liver; immune response; disease; NECROSIS-FACTOR-ALPHA; INDUCED LIVER-INJURY; C VIRUS-INFECTION; CD8(+) T-CELLS; HLA CLASS-I; B-VIRUS; OXIDATIVE STRESS; BACTERIAL-INFECTION; IDIOSYNCRATIC HEPATOTOXICITY; NEUTRALIZING ANTIBODIES;
D O I
10.1177/1091581819898399
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The liver is primarily thought of as a metabolic organ; however, the liver is also an important mediator of immunological functions. Key perspectives on this emerging topic were presented in a symposium at the 2018 annual meeting of the American College of Toxicology entitled "Beyond metabolism: Role of the immune system in hepatic toxicity." Viral hepatitis is an important disease of the liver for which insufficient preventive vaccines exist. Host immune responses inadequately clear these viruses and often potentiate immunological inflammation that damages the liver. In addition, the liver is a key innate immune organ against bacterial infection. Hepatocytes and immune cells cooperatively control systemic and local bacterial infections. Conversely, bacterial infection can activate multiple types of immune cells and pathways to cause hepatocyte damage and liver injury. Finally, the immune system and specifically cytokines and drugs can interact in idiosyncratic drug-induced liver injury. This rare disease can result in a disease spectrum that ranges from mild to acute liver failure. The immune system plays a role in this disease spectrum.
引用
收藏
页码:151 / 164
页数:14
相关论文
共 144 条
[1]  
Aghaeepour N, 2017, SCI IMMUNOL, V1, P2
[2]   HUMAN C'3 - EVIDENCE FOR LIVER AS PRIMARY SITE OF SYNTHESIS [J].
ALPER, CA ;
JOHNSON, AM ;
BIRTCH, AG ;
MOORE, FD .
SCIENCE, 1969, 163 (3864) :286-&
[3]   An update on HDV: virology, pathogenesis and treatment [J].
Alvarado-Mora, Monica V. ;
Locarnini, Stephen ;
Rizzetto, Mario ;
Rebello Pinho, Joao R. .
ANTIVIRAL THERAPY, 2013, 18 (03) :541-548
[4]   Activation of STAT1 is required for interferon-alpha-mediated cell death [J].
Arulampalam, Velmurugesan ;
Kolosenko, Iryna ;
Hjortsbert, Linn ;
Bjorklund, Ann-Charlotte ;
Grander, Dan ;
Tamm, Katja Pokrovskaja .
EXPERIMENTAL CELL RESEARCH, 2011, 317 (01) :9-19
[5]   Klebsiella pneumoniae Yersiniabactin Promotes Respiratory Tract Infection through Evasion of Lipocalin 2 [J].
Bachman, Michael A. ;
Oyler, Jennifer E. ;
Burns, Samuel H. ;
Caza, Melissa ;
Lepine, Francois ;
Dozois, Charles M. ;
Weiser, Jeffrey N. .
INFECTION AND IMMUNITY, 2011, 79 (08) :3309-3316
[6]   NKT cell subsets as key participants in liver physiology and pathology [J].
Bandyopadhyay, Keya ;
Marrero, Idania ;
Kumar, Vipin .
CELLULAR & MOLECULAR IMMUNOLOGY, 2016, 13 (03) :337-346
[7]   Zidovudine (AZT) and Hepatic Lipid Accumulation: Implication of Inflammation, Oxidative and Endoplasmic Reticulum Stress Mediators [J].
Banerjee, Atrayee ;
Abdelmegeed, Mohamed A. ;
Jang, Sehwan ;
Song, Byoung-Joon .
PLOS ONE, 2013, 8 (10)
[8]   T-CELL SUBSETS IN THE HYPORESPONSIVENESS TO HEPATITIS-B SURFACE-ANTIGEN (HBSAG) AND ANTIGEN-SPECIFIC SUPPRESSOR LYMPHOCYTES IN CHRONIC HEPATITIS-B VIRUS (HBV) INFECTION [J].
BARNABA, V ;
LEVRERO, M ;
VANDYKE, AD ;
MUSCA, A ;
CORDOVA, C ;
BALSANO, F .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1985, 34 (03) :284-295
[9]   Trovafloxacin-induced replication stress sensitizes HepG2 cells to tumor necrosis factor-alpha-induced cytotoxicity mediated by extracellular signal-regulated kinase and ataxia telangiectasia and Rad3-related [J].
Beggs, Kevin M. ;
Maiuri, Ashley R. ;
Fullerton, Aaron M. ;
Poulsen, Kyle L. ;
Breier, Anna B. ;
Ganey, Patricia E. ;
Roth, Robert A. .
TOXICOLOGY, 2015, 331 :35-46
[10]   Molecular Mechanisms of Hepatocellular Apoptosis Induced by Trovafloxacin-Tumor Necrosis Factor-alpha Interaction [J].
Beggs, Kevin M. ;
Fullerton, Aaron M. ;
Miyakawa, Kazuhisa ;
Ganey, Patricia E. ;
Roth, Robert A. .
TOXICOLOGICAL SCIENCES, 2014, 137 (01) :91-101