The role of Kupffer cells in hepatic diseases

Li, Peizhi; He, Kun; Li, Jinzheng; Liu, Zuojin; Gong, Jianping

doi:10.1016/j.molimm.2017.02.018

Cited by 168 publications

(129 citation statements)

References 70 publications

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“…Given their hepatic residence, KCs are exposed to a rich supply of nutrients, invading pathogens and bacteria, and exogenous drugs and toxins. Various substances, including LPS, complement factors, fungi, and bacteria, activate KCs (72).…”

Section: Tissue Mɸs Regulate Iron Homeostasis and Tissue Functionmentioning

confidence: 99%

Regulation of tissue iron homeostasis: the macrophage “ferrostat”

Winn¹,

Volk²,

Hasty³

2020

JCI Insight

121

113

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Section: Tissue Mɸs Regulate Iron Homeostasis and Tissue Functionmentioning

confidence: 99%

Regulation of tissue iron homeostasis: the macrophage “ferrostat”

Winn¹,

Volk²,

Hasty³

2020

JCI Insight

121

113

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“…KCs have receptors for pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) [48]. Lipopolysaccharide (LPS) is an example of Gram-negative bacteria-derived PAMP that triggers KC activation by activation of toll-like receptor (TLR) 4 [49].…”

Section: Perivascular Cells In Liver Injurymentioning

confidence: 99%

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

Meirelles

Marson

Solari³

et al. 2020

Cells

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Cirrhosis, a late form of liver disease, is characterized by extensive scarring due to exacerbated secretion of extracellular matrix proteins by myofibroblasts that develop during this process. These myofibroblasts arise mainly from hepatic stellate cells (HSCs), liver-specific pericytes that become activated at the onset of liver injury. Consequently, HSCs tend to be viewed mainly as myofibroblast precursors in a fibrotic process driven by inflammation. Here, the molecular interactions between liver pericytes and inflammatory cells such as macrophages and neutrophils at the first moments after injury and during the healing process are brought into focus. Data on HSCs and pericytes from other tissues indicate that these cells are able to sense pathogen- and damage-associated molecular patterns and have an important proinflammatory role in the initial stages of liver injury. On the other hand, further data suggest that as the healing process evolves, activated HSCs play a role in skewing the initial proinflammatory (M1) macrophage polarization by contributing to the emergence of alternatively activated, pro-regenerative (M2-like) macrophages. Finally, data suggesting that some HSCs activated during liver injury could behave as hepatic progenitor or stem cells will be discussed.

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“…Kupffer cells (KCs) are the liver-derived macrophages that represent approximately 80–90% of the tissue resident macrophages [12, 13]. KCs have been implicated in the pathogenesis of various liver diseases, such as NASH, alcoholic liver disease and liver fibrosis, and are thought to contribute to liver rejection after transplantation [14–16]. KCs have been described as the primary site of NLRP3 inflammasome activation and the source of the pro-inflammatory cytokine IL-1β in liver tissues [17].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease development

Zhu

Liu

et al. 2017

Oncotarget

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NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1β (IL-1β) secretion in Kupffer cells (KCs). However, the specific mechanism of the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3 on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP−/− (thioredoxin-interacting protein) and NLRP3−/− mice, and isolated KCs. We found that the expressions of NLRP3 and TXNIP in human liver tissues were higher in NASH group than in NAFL group. Furthermore, co-immunoprecipitation analyses show that activation of the TXNIP-NLRP3 inflammasome protein complex occurred in KCs of NASH WT mice rather than NAFL WT mice, thus suggesting that the formation and activation of this protein complex is mainly involved in the development of NASH. NLRP3−/− mice exhibited less severe NASH than WT mice in MCD diet model, whereas TXNIP deficiency enhanced NLRP3 inflammasome activation and exacerbated liver injury. PA triggered the activation and co-localization of the NLRP3 inflammasome protein complex in KCs isolated from WT and TXNIP−/− but not NLRP3−/− mice, and most of the complex co-localized with mitochondria of KCs following PA stimulation. Taken together, our novel findings indicate that TXNIP plays a protective and anti-inflammatory role in the development of NAFLD through binding and suppressing NLRP3.

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The role of Kupffer cells in hepatic diseases

Cited by 168 publications

References 70 publications

Regulation of tissue iron homeostasis: the macrophage “ferrostat”

Regulation of tissue iron homeostasis: the macrophage “ferrostat”

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair

Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease development

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