Semin Liver Dis 2010; 30(2): 186-194
DOI: 10.1055/s-0030-1253227
© Thieme Medical Publishers

The Role of Inflammation in Cholestasis: Clinical and Basic Aspects

Astrid Kosters1 , Saul J. Karpen1
  • 1Texas Children's Liver Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
Further Information

Publication History

Publication Date:
26 April 2010 (online)

ABSTRACT

Hepatobiliary transport systems are essential for the uptake and excretion of a variety of compounds including bile acids. Disruption and dysregulation of this excretory pathway result in cholestasis, leading to the intrahepatic accumulation of bile acids and other toxic compounds with progression of liver pathology. Cholestasis induced by inflammation is a common complication in patients with extrahepatic infections or inflammatory processes, generally referred to as sepsis-associated cholestasis. Microbial products, including endotoxin, induce signaling pathways within hepatocytes either directly, or through activation of proinflammatory cytokines, leading to rapid and profound reductions in bile flow. The expression and function of key hepatobiliary transporters are suppressed in response to inflammatory signaling. These proinflammatory signaling cascades lead to repressed expression and activity of a large number of nuclear transcriptional regulators, many of which are essential for maintenance of hepatobiliary transporter gene expression. Interestingly, recently discovered molecular crosstalk between bile acid activated nuclear receptors and proinflammatory nuclear mediators may provide new means of understanding adaptive processes within liver. Inflammation-induced cholestasis and the effects of retained molecules in cholestasis on inflammatory signals are interwoven in the liver, providing potential opportunities for research and therapeutics.

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Saul J KarpenM.D. Ph.D. 

Texas Children's Liver Center, Department of Pediatrics/GI, Hepatology, and Nutrition

Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030

Email: skarpen@bcm.tmc.edu

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