Role of inflammation and proinflammatory cytokines in cholangiocyte pathophysiology

Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt B):1270-1278. doi: 10.1016/j.bbadis.2017.07.024. Epub 2017 Jul 25.

Abstract

Cholangiocytes, the epithelial cells lining the bile ducts, are an important subset of liver cells. They are involved in the modification of bile volume and composition, and respond to endogenous and exogenous stimuli. Along the biliary tree, two different kinds of cholangiocytes exist: small and large cholangiocytes. Each type has different features and biological role in physiologic and pathologic conditions, and their immunobiology is important for understanding biliary diseases. Cholangiocytes provide the first line of defence against luminal microbes in the hepatobiliary system. Indeed, they express a variety of pattern recognition receptors and may start an antimicrobial defence activating a set of intracellular signalling cascades. In response to injury, cholangiocytes that are normally quiescent become reactive and acquire a neuroendocrine-like phenotype with the release of proinflammatory mediators and antimicrobial peptides, which support biliary epithelial integrity. These molecules act in an autocrine/paracrine manner to modulate cholangiocyte biology and determine the evolution of biliary damage. Failure or dysregulation of such mechanisms may influence the progression of cholangiopathies, a group of diseases that selectively target biliary cells. In this review, we focus on the response of cholangiocytes in inflammatory conditions, with a particular focus on the mechanism driving cholangiocytes adaptation to damage. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Keywords: Cholangiocytes; Inflammasome; Inflammation; PBC; PSC.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile / metabolism
  • Bile / microbiology
  • Bile Duct Neoplasms / etiology*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts / cytology
  • Bile Ducts / microbiology
  • Bile Ducts / physiology
  • Carcinogenesis / immunology
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cholangiocarcinoma / etiology*
  • Cholangiocarcinoma / pathology
  • Cholangitis / etiology*
  • Cholangitis / pathology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Progression
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology*
  • Gastrointestinal Microbiome / physiology
  • Humans
  • Signal Transduction / physiology

Substances

  • Cytokines