Kupffer cells regulate liver recovery through induction of chemokine receptor CXCR2 on hepatocytes after acetaminophen overdose in mice

Nguyen, Nga; Umbaugh, David S.; Sánchez-Guerrero, Giselle; Ramachandran, Anup; Jaeschke, Hartmut

doi:10.1007/s00204-021-03183-0

Cited by 31 publications

(22 citation statements)

References 74 publications

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“…Functionally, KCs play protective and pro-repairing roles in APAP-liver injury, since KCs depletion leads to more serious injury and slower recovery ( 14 ) ( Figure 2 ). The underlying mechanisms include: First, KCs promote hepatocytes survival via IL10 ( 46 ). Second, KCs facilitate tissue repair through regulating extracellular matrix (ECM) remodeling.…”

Section: Kc In Acute Liver Injurymentioning

confidence: 99%

Heterogeneity and Function of Kupffer Cells in Liver Injury

Chang

2022

Front. Immunol.

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Kupffer cells (KCs) are key regulators of liver immunity composing the principal part of hepatic macrophages even body tissue macrophages. They reside in liver sinusoids towards portal vein. The micro-environment shapes KCs unique immunosuppressive features and functions. KCs express specific surface markers that distinguish from other liver macrophages. By engulfing gut-derived foreign products and apoptotic cells without triggering excessive inflammation, KCs maintain homeostasis of liver and body. Heterogeneity of KCs has been identified in different studies. In terms of the origin, adult KCs are derived from progenitors of both embryo and adult bone marrow. Embryo-derived KCs compose the majority of KCs in healthy and maintain by self-renewal. Bone marrow monocytes replenish massively when embryo-derived KC proliferation are impaired. The phenotype of KCs is also beyond the traditional dogma of M1-M2. Functionally, KCs play central roles in pathogenesis of acute and chronic liver injury. They contribute to each pathological stage of liver disease. By initiating inflammation, regulating fibrosis, cirrhosis and tumor cell proliferation, KCs contribute to the resolution of liver injury and restoration of tissue architecture. The underlying mechanism varied by damage factors and pathology. Understanding the characteristics and functions of KCs may provide opportunities for the therapy of liver injury. Herein, we attempt to afford insights on heterogeneity and functions of KCs in liver injury using the existing findings.

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Section: Kc In Acute Liver Injurymentioning

confidence: 99%

Heterogeneity and Function of Kupffer Cells in Liver Injury

Chang

2022

Front. Immunol.

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“…While through the secretion of IL-10, KCs can influence CXCR2 expression and pro-regenerative gene expression in surviving hepatocytes. Thus, KCs assist hepatocytes in shifting near the necrosis region to a proliferative state [ 60 ]. These studies suggest the resident KCs could prevent APAP impairment and promote liver restoration through secreted cytokines and chemokines.…”

Section: The Dual Role Of Immune Cells and Cytokinesmentioning

confidence: 99%

“…Depletion of KCs can lead to liver injury aggravation [54][55][56]. KCs against AILI by secreting cytokines [57][58][59][60] MoMFs…”

Section: Neutrophilsmentioning

confidence: 99%

The Dual Role of Innate Immune Response in Acetaminophen-Induced Liver Injury

Yang

Wang

et al. 2022

Biology

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Acetyl-para-aminophenol (APAP), a commonly used antipyretic analgesic, is becoming increasingly toxic to the liver, resulting in a high rate of acute hepatic failure in Europe and the United States. Excessive APAP metabolism in the liver develops an APAP–protein adduct, which causes oxidative stress, mitochondrial membrane permeability, and hepatic necrosis. HMGB-1, HSP, nDNA, mtDNA, uric acid, and ATP are DMAPs released during hepatic necrosis. DMAPs attach to TLR4-expressing immune cells such KCs, macrophages, and NK cells, activating them and causing them to secrete cytokines. Immune cells and their secreted cytokines have been demonstrated to have a dual function in acetaminophen-induced liver injury (AILI), with a role in either proinflammation or pro-regeneration, resulting in contradicting findings and some research confusion. Neutrophils, KCs, MoMFs, NK/NKT cells, γδT cells, DCs, and inflammasomes have pivotal roles in AILI. In this review, we summarize the dual role of innate immune cells involved in AILI and illustrate how these cells initiate innate immune responses that lead to persistent inflammation and liver damage. We also discuss the contradictory findings in the literature and possible protocols for better understanding the molecular regulatory mechanisms of AILI.

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“…As an immune organ, the liver is enriched with a large number of innate immune cells, such as neutrophils, Kupffer cells (KCs), dendritic cells (DCs), and natural killer cells (NKs), as well as adaptive immune cells, such as T cells and B cells. Evidence demonstrates that the immune response is closely linked to the development of drug-induced liver injury (DILI) ( Jiang et al, 2020 ; Nguyen et al, 2022 ).…”

Section: The Mechanisms Of Tp-induced Hepatotoxicitymentioning

confidence: 99%

The molecular pathogenesis of triptolide-induced hepatotoxicity

Wang

et al. 2022

Front. Pharmacol.

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Triptolide (TP) is the major pharmacologically active ingredient and toxic component of Tripterygium wilfordii Hook. f. However, its clinical potential is limited by a narrow therapeutic window and multiple organ toxicity, especially hepatotoxicity. Furthermore, TP-induced hepatotoxicity shows significant inter-individual variability. Over the past few decades, research has been devoted to the study of TP-induced hepatotoxicity and its mechanism. In this review, we summarized the mechanism of TP-induced hepatotoxicity. Studies have demonstrated that TP-induced hepatotoxicity is associated with CYP450s, P-glycoprotein (P-gp), oxidative stress, excessive autophagy, apoptosis, metabolic disorders, immunity, and the gut microbiota. These new findings provide a comprehensive understanding of TP-induced hepatotoxicity and detoxification.

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Kupffer cells regulate liver recovery through induction of chemokine receptor CXCR2 on hepatocytes after acetaminophen overdose in mice

Cited by 31 publications

References 74 publications

Heterogeneity and Function of Kupffer Cells in Liver Injury

Heterogeneity and Function of Kupffer Cells in Liver Injury

The Dual Role of Innate Immune Response in Acetaminophen-Induced Liver Injury

The molecular pathogenesis of triptolide-induced hepatotoxicity

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