The Role of Bile Acid‐Mediated Inflammation in Cholestatic Liver Injury

Cai, Shi‐Ying; Li, Man; Boyer, James L.

doi:10.1002/9781119436812.ch56

Cited by 5 publications

(6 citation statements)

References 101 publications

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“…Importantly, we observed total bacterial elimination when dHL-60s are treated with MACF–PHMB hydrogels and used against S. aureus (Figure ). Although the neutrophil peripheral lifespan is a debated subject, some researchers have reported that inflammatory signaling attracts more neutrophil populations to the injury site. , Therefore, with oxygen and PHMB acting as inflammatory signals, , this synergistic treatment might recruit more neutrophils to the site in favor of antibacterial characteristics and applications.…”

Section: Discussionmentioning

confidence: 99%

Modulatory Contribution of Oxygenating Hydrogels and Polyhexamethylene Biguanide on the Antimicrobial Potency of Neutrophil-like Cells

Abri

Attia

Pukale

et al. 2022

ACS Biomater. Sci. Eng.

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Neutrophils are a first line of host defense against infection and utilize a series of oxygen-dependent processes to eliminate pathogens. Research suggests that oxygen availability can improve anti-infective mechanisms by promoting the formation of reactive oxygen species. Also, oxygen can synergistically upregulate the antibacterial properties of certain antibiotics against bacteria by altering their metabolism and causing an increase in the antibiotic uptake of bacteria. Therefore, understanding the effects of oxygen availability, as provided via a biomaterial treatment alone or along with potent antibacterial agents, on neutrophil functions can lead us to the development of new anti-inflammatory and anti-infective approaches. However, the study of neutrophil functions in vitro is often limited by their short life span and nonreproducibility, which suggests the need for cell line-based models as a substitute for primary neutrophils. Here, we took advantage of the differentiated human leukemia-60 cell line (HL-60), as an in vitro neutrophil model, to test the effects of local oxygen and antibacterial delivery by fluorinated methacrylamide chitosan (MACF) hydrogels incorporated with polyhexamethylene biguanide (PHMB) antibacterial agent. Considering the natural modes of neutrophil actions to combat bacteria, we studied the impact of our dual functioning oxygenating-antibacterial platforms on neutrophil phagocytosis and antibacterial properties as well as the formation of neutrophil extracellular traps (NETs) and reactive oxygen species (ROS). Our results demonstrated that supplemental oxygen and antibacterial delivery from MACF–PHMB hydrogel platforms upregulated neutrophil antibacterial properties and ROS production. NET formation by neutrophils upon treatment with MACF and PHMB varied when chemical and biological stimuli were used. Overall, this study presents a model to study immune responses in vitro and lays the foundation for future studies to investigate if similar responses also occur in vivo.

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Section: Discussionmentioning

confidence: 99%

Modulatory Contribution of Oxygenating Hydrogels and Polyhexamethylene Biguanide on the Antimicrobial Potency of Neutrophil-like Cells

Abri

Attia

Pukale

et al. 2022

ACS Biomater. Sci. Eng.

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“…The physiological consequences of reduced intestinal BAs cause maldigestion of triacylglycerol and malabsorption of fat-soluble vitamins. The pathophysiological level of BAs induces inflammation [ 53 ]. If untreated, increased circulating BAs cause pruritus, and can eventually cause apoptosis or necrosis of hepatocytes, leading to progressive hepatic fibrosis and even cirrhosis that can cause death due to hepatic failure or the complications of portal hypertension [ 52 , 54 , 55 ].…”

Section: Cholestatic Liver Diseasementioning

confidence: 99%

“…Pathophysiological levels of BAs induce the production of proinflammatory mediators in hepatocytes that initiate inflammation and trigger cholestatic liver injury [ 53 ]. However, uncontrolled inflammatory processes can induce further liver injury by damaging the local tissue through the release of soluble mediators and deleterious factors.…”

Section: Potential Role Of Vitamin K On Cholestatic Liver Diseasementioning

confidence: 99%

The Role of Vitamin K in Cholestatic Liver Disease

2021

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Vitamin K (VK) is a ligand of the pregnane X receptor (PXR), which plays a critical role in the detoxification of xenobiotics and metabolism of bile acids. VK1 may reduce the risk of death in patients with chronic liver failure. VK deficiency is associated with intrahepatic cholestasis, and is already being used as a drug for cholestasis-induced liver fibrosis in China. In Japan, to treat osteoporosis in patients with primary biliary cholangitis, VK2 formulations are prescribed, along with vitamin D3. Animal studies have revealed that after bile duct ligation-induced cholestasis, PXR knockout mice manifested more hepatic damage than wild-type mice. Ligand-mediated activation of PXR improves biochemical parameters. Rifampicin is a well-known human PXR ligand that has been used to treat intractable pruritus in severe cholestasis. In addition to its anti-cholestatic properties, PXR has anti-fibrotic and anti-inflammatory effects. However, because of the scarcity of animal studies, the mechanism of the effect of VK on cholestasis-related liver disease has not yet been revealed. Moreover, the application of VK in cholestasis-related diseases is controversial. Considering this background, the present review focuses on the effect of VK in cholestasis-related diseases, emphasizing its function as a modulator of PXR.

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“…At the same time, there are few studies that have focused on studying hematological inflammatory markers in intrahepatic cholestasis of pregnancy [3]. Considering that bile acids are cytotoxic substances; their high values induce the release of proinflammatory mediators [15]. Some authors suggest that in ICP, women experience specific changes in hematological inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width -standard deviation (RDW-SD) and red cell distribution width -coefficient of variation (RDW-CV), although the results are inconclusive.…”

Section: Introductionmentioning

confidence: 99%

Assessment of the role of hematological inflammatory markers in the severity of intrahepatic cholestasis of pregnancy

Cemortan¹,

Cernetchi²

2022

MJHS

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Introduction. Hematological inflammatory markers may be promising diagnostic markers for assessing the severity of intrahepatic cholestasis of pregnancy. The aim of the study was to evaluate and compare the levels of hematological inflammatory markers in intrahepatic cholestasis of pregnancy. Material and methods. A prospective cohort study of 142 clinical cases, divided into two groups depending on the presence of cholestasis gravidarum, was carried out. The research was conducted by assessing the level of bile acids and hematological inflammatory markers in the mother’s blood, as well as by studying medical records. The IBM Statistics SPSS 21 program was used to process the statistical data. To compare categorical variables, the χ² without the Yates’ continuity correction test was applied. Results. There was an increase in platelet-to-lymphocyte ratio in pregnant women with intrahepatic cholestasis of pregnancy compared to the control group (146.0±6.8 versus 135.2±7.3, respectively). The values of neutrophil-to-lymphocyte ratio and the average volume of platelets were similar in both groups. At the same time, the study found a decrease in the values of erythrocyte distribution among women whose pregnancy was complicated by cholestasis gravidarum. Conclusions. The study showed a significant increase in platelet-to-lymphocyte ratio in women whose pregnancy was complicated by cholestasis gravidarum, as well as an increase in this indicator with increasing levels of bile acids. Thus, this ratio may be a promising diagnostic marker in assessing the severity of intrahepatic cholestasis of pregnancy.

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The Role of Bile Acid‐Mediated Inflammation in Cholestatic Liver Injury

Cited by 5 publications

References 101 publications

Modulatory Contribution of Oxygenating Hydrogels and Polyhexamethylene Biguanide on the Antimicrobial Potency of Neutrophil-like Cells

Modulatory Contribution of Oxygenating Hydrogels and Polyhexamethylene Biguanide on the Antimicrobial Potency of Neutrophil-like Cells

The Role of Vitamin K in Cholestatic Liver Disease

Assessment of the role of hematological inflammatory markers in the severity of intrahepatic cholestasis of pregnancy

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