Kupffer Cells

Abstract

Chronic alcohol consumption is linked to the development of alcohol-associated liver disease (ALD). This disease is characterized by a clinical spectrum ranging from steatosis to hepatocellular carcinoma. Several cell types are involved in ALD progression, including hepatic macrophages. Kupffer cells (KCs) are the resident macrophages of the liver involved in the progression of ALD by activating pathways that lead to the production of cytokines and chemokines. In addition, KCs are involved in the production of reactive oxygen species. Reactive oxygen species are linked to the induction of oxidative stress and inflammation in the liver. These events are activated by the bacterial endotoxin, lipopolysaccharide, that is released from the gastrointestinal tract through the portal vein to the liver. Lipopolysaccharide is recognized by receptors on KCs that are responsible for triggering several pathways that activate proinflammatory cytokines involved in alcohol-induced liver injury. In addition, KCs activate hepatic stellate cells that are involved in liver fibrosis. Novel strategies to treat ALD aim at targeting Kupffer cells. These interventions modulate Kupffer cell activation or macrophage polarization. Evidence from mouse models and early clinical studies in patients with ALD injury supports the notion that pathogenic macrophage subsets can be successfully translated into novel treatment options for patients with this disease.

Coleus vettiveroides ethanolic root extract protects against thioacetamide‐induced acute liver injury in rats

“…It is a well‐established fact that liver injury due to oxidative stress and hepatic inflammation plays a vital role in the development and progression of acute liver disease 51,52 . Under adverse conditions such as injury, liver‐resident macrophages, called Kupffer cells, secrete pro‐inflammatory cytokines, which initiate hepatic inflammation 53,54 . Activation of various inflammatory pathways plays a crucial role in liver injury progression.…”

“…Similarly, our results demonstrate that CVERE could prevent TAA-induced membrane permeability mediated by LPO and oxidative burden, as evidenced by decreased oxidative stress markers and improved antioxidants.It is a well-established fact that liver injury due to oxidative stress and hepatic inflammation plays a vital role in the development and progression of acute liver disease 51,52. Under adverse conditions such as injury, liver-resident macrophages, called Kupffer cells, secrete pro-inflammatory cytokines, which initiate hepatic inflammation 53,54. Activation of various inflammatory pathways plays a crucial role in liver injury progression.…”

Phosphate Groups in the Lipid A Moiety Determine the Effects of LPS on Hepatic Stellate Cells: A Role for LPS-Dephosphorylating Activity in Liver Fibrosis

“…During chronic liver diseases, gut-derived LPS is known to promote fibrogenic activity [ 25 , 40 , 41 ]. Because of increased permeability of the intestinal wall, associated with high levels of permeability-enhancing factors in the circulation, increased levels of LPS and other bacterial products enter the portal circulation [ 42 ].…”

Modulação da microbiota intestinal em indivíduos alcoolistas: uma revisão narrativa

“…Tal fato aumenta a concentração de espécies reativas de oxigênio, bem como de TNF-α, o qual atua como principal mediador da resposta inflamatória. Uma das estratégias para o tratamento dessas doenças tem sido pautada na eliminação dessas células reativas para minimizar o estresse oxidativo metabólico nos hepatócitos (Slevin et al, 2020). Pacientes alcoolistas apresentaram um aumento dos níveis plasmáticos de interleucina 8 (IL-8) que possui um efeito pró-inflamatório (Leclercq et al, 2014).…”