Cited by 1,295Liver physiology and pathologyLiver Disease Diagnosis and TreatmentLiver Diseases and Immunity

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Liver inflammation and fibrosis

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Koyama, Yukinori, Brenner, David A.·2017·Journal of Clinical Investigation

DOI 10.1172/jci88881PMC PMC5199698

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Abstract

Chronic liver inflammation leads to fibrosis and cirrhosis, which is the 12th leading cause of death in the United States. Hepatocyte steatosis is a component of metabolic syndrome and insulin resistance. Hepatic steatosis may be benign or progress to hepatocyte injury and the initiation of inflammation, which activates immune cells. While Kupffer cells are the resident macrophage in the liver, inflammatory cells such as infiltrating macrophages, T lymphocytes, neutrophils, and DCs all contribute to liver inflammation. The inflammatory cells activate hepatic stellate cells, which are the major source of myofibroblasts in the liver. Here we review the initiation of inflammation in the liver, the liver inflammatory cells, and their crosstalk with myofibroblasts.

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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Background
NLRP3 activation in neutrophils induces lethal autoinflammation, liver inflammation, and fibrosis
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Influential
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Background
Role of NLRP3 inflammasome in liver disease
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“Our observation that more inflammatory aggregates were found at 18 weeks of FFD feeding compared to 28 weeks supports the view that hepatic inflammation is dynamic and that advanced stages of NASH may have less inflammation than earlier stages as reported by Koyama and Brenner [42].”
Result
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“These immune cells release ROS to combat pathogens and repair damage, but excessive ROS can lead to hepatocyte injury and promote fibrosis (Koyama and Brenner 2017).”
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Background
Nrf2/ HO ‐1, NF‐κB and PI3K /Akt signalling pathways decipher the therapeutic mechanism of pitavastatin in early phase liver fibrosis in rats
Elbaset, M. A., Mohamed, B. M. S. A., Hessin, A. F., El‐Rahman, S. S. A., Esatbeyoglu, T., Afifi, S. M., & Fayed, H. M. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18116 · Cited by 41
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Heterogeneous Iron Oxide/Dysprosium Oxide Nanoparticles Target Liver for Precise Magnetic Resonance Imaging of Liver Fibrosis
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BackgroundInfluential
Specialized Proresolving Mediators for Therapeutic Interventions Targeting Metabolic and Inflammatory Disorders
Han, Y., KyeongJin, L., Saha, A., Han, J., Choi, H., Noh, M., Lee, Y., & Lee, M. (2021) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2021.094 · Cited by 43
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The histone demethylase KDM4D promotes hepatic fibrogenesis by modulating Toll-like receptor 4 signaling pathway
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GARP on hepatic stellate cells is essential for the development of liver fibrosis
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Hot and cold fibrosis: The role of serum biomarkers to assess immune mechanisms and ECM-cell interactions in human fibrosis
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“In addition, hepatic inflammatory cells include activated T lymphocytes such as CD4+CD44+ and CD8+CD44+ cells [41].”
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Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-κB/HIF-1α Pathway in CCl 4 -Induced Liver Fibrosis
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EphB2 receptor tyrosine kinase promotes hepatic fibrogenesis in mice via activation of hepatic stellate cells
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“LPS or free fatty acid could activate a M1 phenotype and release of inflammation cytokines through TLR4 signal pathway (Koyama and Brenner, 2017).”
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High-Sensitive CRP Correlates With the Severity of Liver Steatosis and Fibrosis in Obese Patients With Metabolic Dysfunction Associated Fatty Liver Disease
Zhu, C., Huang, D., Ma, H., Qian, C., You, H., Bu, L., & Qu, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.848937 · Cited by 40
“(42) reviewed the close association among obesity, hepatic inflammation, and the development of NAFLD, which can progress to nonalcoholic steatohepatitis, fibrosis, and eventually cirrhosis due to sequential activation of inflammatory cascade (10).”
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Central role for cholangiocyte pathobiology in cholestatic liver diseases
Jalan-Sakrikar, N., Guicciardi, M. E., O’Hara, S. P., Azad, A., LaRusso, N. F., Gores, G. J., & Huebert, R. C. (2025) · Hepatology · doi:10.1097/hep.0000000000001093 · Cited by 38
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“Liver Fibrosis Repetitive injury or inflammation due to NAFLD/NASH causes scarring of liver tissue or fibrosis (73, 74).”
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The Extra Virgin Olive Oil Polyphenol Oleocanthal Exerts Antifibrotic Effects in the Liver
Gabbia, D., Carpi, S., Sarcognato, S., Cannella, L., Colognesi, M., Scaffidi, M., Polini, B., Digiacomo, M., Salsano, J. E., Manera, C., et al. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.715183 · Cited by 37
“Moreover, since CCL2 and its receptor CCR2 control the infiltration ofmonocytes into the liver (62), we can hypothesize that OC interferes with the hepatic recruitment of these cells, to reduce inflammation.”
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Potential Roles and Key Mechanisms of Hawthorn Extract against Various Liver Diseases
Kim, E., Jang, E., & Lee, J. (2022) · Nutrients · doi:10.3390/nu14040867 · Cited by 39
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The versatility of macrophage heterogeneity in liver fibrosis
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“A series of cellular and molecular responses could cause pathological changes including death of parenchymal cells and deposition of ECM in the liver (1).”
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Serum interleukin-34 level can be an indicator of liver fibrosis in patients with chronic hepatitis B virus infection
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PCAF fine‐tunes hepatic metabolic syndrome, inflammatory disease, and cancer
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c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis
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Limonin Alleviates Non-alcoholic Fatty Liver Disease by Reducing Lipid Accumulation, Suppressing Inflammation and Oxidative Stress
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“A large number of experimental and clinical data support that inflammatory cells, especially macrophages, play a central role Frontiers in Pharmacology | www.frontiersin.org January 2022 | Volume 12 | Article 8017308 in the occurrence and development of NAFLD and NASH (Koyama and Brenner, 2017).”
BackgroundInfluential
Polyunsaturated fatty acids drive neutrophil extracellular trap formation in nonalcoholic steatohepatitis
Wu, J., Zhang, C., He, T., Zhang, S., Wang, Y., Xie, Z., Xu, W., Ding, C., Shuai, Y., Hao, H., et al. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175618 · Cited by 35
Kupffer Cells: Important Participant of Hepatic Alveolar Echinococcosis
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“KCs Secrete Some Cytokines, and Anti-inflammatory Cytokines Were Expressed at Higher Levels Than Pro-inflammatory Cytokines in Patients With Hepatic AE CD68 is commonly used as a surface marker for KCs in human (Sica et al., 2014; Koyama and Brenner, 2017), during liver tissue self-repair stage, KCs highly express CD1…”
Background
Activation of BK Channels Prevents Hepatic Stellate Cell Activation and Liver Fibrosis Through the Suppression of TGFβ1/SMAD3 and JAK/STAT3 Profibrotic Signaling Pathways
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“BK Channel Activation Attenuates Liver Fibrosis Through Inhibition of the TGFβ1/SMAD3 and JAK2/STAT3 Signaling Pathways Several studies have shown that TGFβ1 plays pivotal roles in HSC activation and hepatic fibrosis (Koyama and Brenner, 2017; Tsuchida and Friedman, 2017).”
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Kefir in the Prevention and Treatment of Obesity and Metabolic Disorders
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Authors: Koyama, Y., & Brenner, D. A.
Affiliations: University of California San Diego (US)
Corresponding author: Brenner, David A.
ORCID: Koyama, Yukinori
Brenner, David A.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2017-01-03
Volume: 127
Issue: 1
Pages: 55-64
ISSN: 0021-9738 (ISSN-L)
1558-8238
DOI: 10.1172/jci88881
PMC: PMC5199698
OpenAlex: W2562949639
Cited by: 1,295
References: 158
Citations by year: 2026: 139 · 2025: 162 · 2024: 159 · 2023: 171 · 2022: 173 · 2021: 177 · 2020: 151 · 2019: 85 · 2018: 63 · 2017: 13
FWCI: 12.30
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (ES010337, AA011999)
National Institute on Alcohol Abuse and Alcoholism (U01AA021856, P50AA011999)
National Institute of Environmental Health Sciences (P42ES010337)
Topics: Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords: liver inflammation, liver fibrosis, liver cirrhosis, hepatic steatosis, Kupffer cells, hepatic stellate cells, myofibroblasts, immune cell crosstalk, T cells, neutrophils, dendritic cells, metabolic syndrome, insulin resistance
MeSH terms: Animals, Dendritic Cells, Hepatitis, Humans, Inflammation, Kupffer Cells, Liver, Liver Cirrhosis, Neutrophils, T-Lymphocytes, Hepatic Stellate Cells, Myofibroblasts

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