Track topics on Twitter Track topics that are important to you
CXC chemokine receptor 2 (CXCR2) is critical for neutrophil recruitment and hepatocellular viability, but has not been studied in the context of cholestatic liver injury following bile duct ligation (BDL). The present study sought to elucidate the cell-specific roles of CXCR2 on acute liver injury after BDL. Wild-type and CXCR2 -/- mice were subjected BDL. CXCR2 chimeric mice were created to assess cell specific role of CXCR2 on liver injury after BDL. SB225002, a selective CXCR2 antagonist, was administrated intraperitoneally after BDL to investigate the potential of pharmacological inhibitor. CXCR2 -/- mice had significant less liver injury than wild-type mice at 3 days and 14 days after BDL. There was no difference in biliary fibrosis among groups. The chemokines CXCL1 and CXCL2 were induced around areas of necrosis and biliary structures, respectively, both areas where neutrophils accumulated after BDL. CXCR2 -/- mice showed significantly less neutrophil accumulation in those injured area. CXCR2 and CXCR2mice recapitulated the wild-type and CXCR2-knockout phenotypes, respectively. CXCR2 mice suffered higher liver injury than CXCR2and CXCR2, however, only those chimeras with knockout of myeloid CXCR2 (CXCR2and CXCR2) showed reduction of neutrophil accumulation around areas of necrosis. Daily administration of SB225002 starting after 3 days of BDL reduced established liver injury at 6 days. In conclusion, neutrophil CXCR2 guides the cell to the site of injury, while CXCR2 on liver cells affects liver damage independent of neutrophil accumulation. CXCR2 appears to be a viable therapeutic target for cholestatic liver injury.
This article was published in the following journal.
Name: American journal of physiology. Gastrointestinal and liver physiology
The frequency of acquired liver injury and failure in critical illness has been significantly increasing over the last decades. Currently, liver injury and failure are observed in up to twenty percent...
Methimazole (MMI) has been used for the treatment of Graves' Disease (GD) for more than half a century. The MMI treatment has been reported to be associated with hepatotoxicity. Previous studies have ...
Fibrosing cholestatic hepatitis (FCH) is an uncommon form of liver injury that often progresses to fulminant liver failure(1). FCH is well-described in immunosuppressed patients, particularly after tr...
Monoacylglycerol lipase (MGL) is the last enzymatic step in triglyceride degradation, hydrolyzing monoglycerides into glycerol and fatty acids (FA) and converting 2-arachidonoylglycerol into arachidon...
Disrupted regulation and accumulation of bile salts (BS) in the liver can contribute towards progressive liver damage and fibrosis. Here, we investigated the role of BS in the progression of cholestat...
The investigators hypothesize that the CXCR2 ligands/CXCR2 biological axis plays an important role in promoting angiogenesis in PC; and that the genetic changes and the microenvironment of...
Cholestatic drug-induced liver injury (DILI) is the severe form of DILI with a grave outcome. Drug-metabolizing enzymes play an important role in the metabolism of drugs. The genetic poly...
This study examines the hypothesis that administering intravenous fish oil, in lieu of intravenous soybean oil, can ameliorate the progression of PN-associated cholestatic liver disease in...
This study is a biobank of specimens and clinical data for use in current and future research to better understand the cholestatic liver diseases primary biliary cirrhosis/cholangitis (PBC...
Taiwan is a hyperendemic area of hepatitis B virus (HBV) infection. Previous studies demonstrated vigorous T cell responses to HBV-encoded antigens developed in patients with self-limited ...
A costimulatory receptor that is specific for INDUCIBLE T-CELL CO-STIMULATOR LIGAND. The receptor is associated with a diverse array of immunologically-related effects including the increased synthesis of INTERLEUKIN 10 in REGULATORY T-LYMPHOCYTES and the induction of PERIPHERAL TOLERANCE.
A human liver tumor cell line used to study a variety of liver-specific metabolic functions.
Sudden liver failure in the presence of underlying compensated chronic LIVER DISEASE (e.g., LIVER CIRRHOSIS; HEPATITIS; and liver injury and failure) due to a precipitating acute hepatic insult.
Extracts of liver tissue containing uncharacterized specific factors with specific activities; a soluble thermostable fraction of mammalian liver is used in the treatment of pernicious anemia.
Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
Cytokines include chemokines, lymphokines, and monokines. Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to...