Increased Expression of Major Histocompatibility Antigens in the Liver as a Result of Cholestasis

Innes, G; Nagafuchi, Yukihisa; Fuller, Barbara; Hobbs, K. E. F.

doi:10.1097/00007890-198804000-00017

Cited by 27 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Liver immunological attack in cholestatic autoimmune diseases occurs by: (i) the existence of an exacerbated immune response caused by the loss of tolerance to autoantigens, and (ii) aberrant overexpression of antigens of both MHC-I (in hepatocytes) [196] and MHC-II (in cholangiocytes) [197].…”

Section: Immunoregulatory Properties Of Udcamentioning

confidence: 99%

Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications

et al. 2011

View full text Add to dashboard Cite

UDCA (ursodeoxycholic acid) is the therapeutic agent most widely used for the treatment of cholestatic hepatopathies. Its use has expanded to other kinds of hepatic diseases, and even to extrahepatic ones. Such versatility is the result of its multiple mechanisms of action. UDCA stabilizes plasma membranes against cytolysis by tensioactive bile acids accumulated in cholestasis. UDCA also halts apoptosis by preventing the formation of mitochondrial pores, membrane recruitment of death receptors and endoplasmic-reticulum stress. In addition, UDCA induces changes in the expression of metabolizing enzymes and transporters that reduce bile acid cytotoxicity and improve renal excretion. Its capability to positively modulate ductular bile flow helps to preserve the integrity of bile ducts. UDCA also prevents the endocytic internalization of canalicular transporters, a common feature in cholestasis. Finally, UDCA has immunomodulatory properties that limit the exacerbated immunological response occurring in autoimmune cholestatic diseases by counteracting the overexpression of MHC antigens and perhaps by limiting the production of cytokines by immunocompetent cells. Owing to this multi-functionality, it is difficult to envisage a substitute for UDCA that combines as many hepatoprotective effects with such efficacy. We predict a long-lasting use of UDCA as the therapeutic agent of choice in cholestasis.

show abstract

Section: Immunoregulatory Properties Of Udcamentioning

confidence: 99%

Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Induction of the expression of class I MHC antigens has also been observed in several liv er diseases of different causes, including alco holic, autoimmune, viral and malignant liver damage [12,13,25]. The expression of class I antigens has recently been observed in inbred rats as a result of cholestasis [26], Induction of the expression of class 1 antigens due to such disparate causes may represent a nonspecific manifestation of hepatocellular injury. The recent report of increased class I expression in diabetes [27] and in neuromuscular dystro phies [28] may indicate a more general role for class I antigens in pathogenic processes.…”

Section: Histological and Immunohistological Studiesmentioning

confidence: 99%

Normothermic Ischemia Induces Major Histocompatibility Complex Class I Expression in Hepatocytes

et al. 1996

View full text Add to dashboard Cite

The hepatic expression of major histocompatibility complex (MHC) antigens is normally limited. However aberrant expression may occur in cholestatic diseases or following liver transplantation. The aim of this work was to investigate the effect of normothermic ischemia on hepatocellular MHC expression. Temporary (90-min) normothermic ischemia of the liver was induced in inbred rats. There was a significant elevation of aspartate aminotransferase and alanine amino-transferase levels after ischemia, rising to their maximum by 6 h. Histologic findings showed large, confluent areas of necrosis, and preserved areas were seen with centrolobular congestion and macrovacuolar steatosis. Expression of MHC class I and II antigens was detected using the immunoperoxidase technique, 1 h, 12 h, 3 days, 7 days and 1 month after the end of intervention. A marked induction of the expression of class I, but not of class II, MHC antigens was observed on the hepatocyte membranes after ischemia. We suggest that normothermic ischemia can occur postoperatively in human liver transplantation and may cause increased expression of class I MHC antigens on hepatocytes, leading to increased sensitivity of liver allografts to rejection by cytotoxic T cells.

show abstract

“…5 In animal experiments, it is also shown that cholestasis itself, which is induced by ligation of the extrahepatic bile duct, leads to an increased expression of MHC class I antigens on hepatocytes in rats. 15 In the other hand, ursodeoxycholic acid (UDCA) is considered to be a nonhepatotoxic hydrophilic bile acid that may reverse the potential hepatotoxicity of endogenous bile acids, and is often used in patients with cholestasis to improve liver dysfunction.16-18 Notably, a beneficial effect of UDCA in patients with PBC has been demonstrated in double-blind controlled studies. [19][20][21] In those studies, UDCA has been shown to improve biochemical parameters.19-21 Calmus et al reported that UDCA significantly decreased MHC class I molecules on hepatocytes in patients with PBC using an immunocytochemistric techniques.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1996

View full text Add to dashboard Cite

We investigated effect of ursodeoxycholic acid on major histocompatibility complex class I gene expression in cultured human hepatoma cells. Ursodeoxycholic acid, which has recently been used for treatment of various autoimmune liver diseases, paradoxically increased mRNA level of major histocompatibility complex class I. However, endogenous bile acids, for example, chenodeoxycholic acid, more strongly increased major histocompatibility complex class I mRNA expression when compared with ursodeoxycholic acid. Concerning interplay between ursodeoxycholic acid and chenodeoxycholic acid, these bile acids additively induced major histocompatibility complex class I mRNA expression. In contrast, when total concentration of ursodeoxycholic acid and chenodeoxycholic acid was kept constant, expression of major histocompatibility complex class I mRNA appeared to be rather decreased in a dose-dependent manner along with increasing ratio of ursodeoxycholic acid.These data might indicate that the beneficial action of ursodeoxycholic acid is related to this relative decrease in major histocompatibility complex class I gene expression.

show abstract

Increased Expression of Major Histocompatibility Antigens in the Liver as a Result of Cholestasis

Cited by 27 publications

References 0 publications

Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications

Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications

Normothermic Ischemia Induces Major Histocompatibility Complex Class I Expression in Hepatocytes

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

Contact Info

Product

Resources

About