Effects of ursodeoxycholic acid and chenodeoxycholic acid on major histocompatibility complex class I gene expression

Hirano, Fuminori; Tanaka, Hirotoshi; Makino, Yuichi; Okamoto, Kensaku; Makino, Isao

doi:10.1007/bf01211187

Cited by 21 publications

(6 citation statements)

References 37 publications

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“…19 However, the effects of bile acids on gene expression are not confined to the process of cholesterol metabolism alone. They are known to affect expression of the histocompatibility genes 20 and activate promoters of genes associated with DNA damage, oxidative stress, endoplasmic reticulum stress, and protein malfolding, 21 as well as modulate activation protein 1 (AP-1) transcription factor abundance and transactivation. 22 This, coupled with the apparent uptake of bile acids by nonhepatic cell types, 4 suggests that they may exert significant effects on multiple biological processes in a variety of different cells, both in cell culture and in vivo.…”

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confidence: 99%

Modulation of steady-state messenger RNA levels in the regenerating rat liver with bile acid feeding

et al. 2001

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Liver regeneration after two thirds partial hepatectomy (PH) is an orchestrated hyperplastic growth process requiring coordinated expression of many genes. The synchronous progression of 95% of the remnant hepatocytes through the cell cycle provides an in vivo model for examining the influence of bile acids on the molecular regulation of hepatocyte replication and growth. In this study, we examined the effects of endogenous deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on messenger RNA (mRNA) expression and growth rate during liver regeneration. Rats were fed diets containing no addition, 0.4% DCA, UDCA, or both for 14 days; they then underwent 70% PH and were maintained on the diets for an additional 14 days. mRNA transcript levels for a variety of cell cycle-regulated genes were examined post-PH by Northern blot analysis. Bile acid concentrations were determined in liver, isolated nuclei, and plasma by gas chromatography and mass spectrometry. The results indicated that the addition of DCA and UDCA to the diet markedly shifted the bile-acid compositions of liver and plasma. In addition, DCA dramatically altered the abundance of many transcripts post-PH, whereas coadministration of UDCA suppressed the effect. DCA feeding significantly inhibited liver growth through day 3; however, by day 8, it induced an approximately 20% increase in mass compared with controls, UDCA-fed, or combination-fed animals. UDCA was concentrated greater than 20-fold in nuclei compared with whole liver in controls and DCAfed animals and greater than 2-fold with UDCA feeding. These data suggest that bile acids may have a key role in liver regeneration, which is significantly altered by modulation of the bile-acid pool. (Liver Transpl 2001;7: 321-334.)

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confidence: 99%

Modulation of steady-state messenger RNA levels in the regenerating rat liver with bile acid feeding

et al. 2001

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“…Proposed UDCA mechanisms that may theoretically fulfill this role include immunomodulation through reduced hepatic expression of human leukocyte antigen (HLA) class 1 and attenuation of cytokine production leading to blunted immune system reactivity. 32 , 33 …”

Section: Resultsmentioning

confidence: 99%

Ursodeoxycholic acid in treatment of non-cholestatic liver diseases: A systematic review

Reardon

Hussaini

Alsahafi

et al. 2016

JCTH

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Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions.Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles.Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded.Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present.

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“…Thus, UDCA suppresses MHC class I and II expression indirectly by reducing the stimulatory influence of hydrophobic bile acids, and also directly by the activation of GR. In this respect UDCA treatment has been shown to significantly reduce HLA class I and II expression in PBC patients 78,79 . This immune modulation may lead to reduced T cell‐mediated cytotoxicity in these patients.…”

Section: Mechanism Of Action Of Ursodeoxycholic Acidmentioning

confidence: 98%

Use of ursodeoxycholic acid in liver diseases

Kumar

Tandon

2001

J of Gastro and Hepatol

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Ursodeoxycholic acid is currently the only established drug for the treatment of chronic cholestatic liver diseases. It has cytoprotective, anti‐apoptotic, membrane stabilizing, anti‐oxidative and immunomodulatory effects. Prolonged administration of ursodeoxycholic acid in patients with primary biliary cirrhosis (PBC) is associated with survival benefit and a delaying of liver transplantation. There is evidence that it might even prevent progression of the histologic stage of PBC. It also has a beneficial effect on primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, liver disease associated with cystic fibrosis, chronic graft versus host disease, total parenteral nutrition associated cholestasis and various pediatric cholestatic liver diseases. In the present review the current knowledge about the mechanisms of the action and role of ursodeoxycholic acid in the treatment of various liver diseases has been discussed.

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Effects of ursodeoxycholic acid and chenodeoxycholic acid on major histocompatibility complex class I gene expression

Cited by 21 publications

References 37 publications

Modulation of steady-state messenger RNA levels in the regenerating rat liver with bile acid feeding

Modulation of steady-state messenger RNA levels in the regenerating rat liver with bile acid feeding

Ursodeoxycholic acid in treatment of non-cholestatic liver diseases: A systematic review

Use of ursodeoxycholic acid in liver diseases

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