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Cholangiopathy with Respect to Biliary Innate Immunity

DOI: 10.1155/2012/793569

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Abstract:

Biliary innate immunity is involved in the pathogenesis of cholangiopathies in cases of biliary disease. Cholangiocytes possess Toll-like receptors (TLRs) which recognize pathogen-associated molecular patterns (PAMPs) and play a pivotal role in the innate immune response. Tolerance to bacterial PAMPs such as lipopolysaccharides is also important to maintain homeostasis in the biliary tree, but tolerance to double-stranded RNA (dsRNA) is not found. Moreover, in primary biliary cirrhosis (PBC) and biliary atresia, biliary innate immunity is closely associated with the dysregulation of the periductal cytokine milieu and the induction of biliary apoptosis and epithelial-mesenchymal transition (EMT), forming in disease-specific cholangiopathy. Biliary innate immunity is associated with the pathogenesis of various cholangiopathies in biliary diseases as well as biliary defense systems. 1. Introduction Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and hepatolithiasis in adults and biliary atresia and choledochal cyst in infants are biliary diseases in which different anatomical levels of the biliary tree are specifically affected and characterized by cholangiopathy. The biliary tree, consisting of cholangiocytes, is a system of connecting ducts that drain the bile secreted by hepatocytes into the duodenum. Cholangiocytes provide the first line of defense in the biliary system against luminal microbes originating from the intestines via portal blood and duodenum [1]. In general, although human bile is normally sterile, it can contain bacterial components such as lipopolysaccharide (LPS), lipoteichoic acid, and bacterial DNA fragments, known as pathogen-associated molecular patterns (PAMPs) [2–5], and cultivable bacteria are detectable in bile of patients with biliary diseases [1, 6–8]. Enteric bacteria, in particular, may be responsible for the chronic proliferative cholangitis associated with hepatolithiasis [1, 6]. These findings indicate that cholangiocytes are exposed to bacterial PAMPs under physiological as well as pathological conditions. Innate immunity was initially thought to be limited to immunocompetent cells such as dendritic cells and macrophages, but epithelial cells also possess TLRs and proper innate immune systems reflecting the specific micro-environment and function of each epithelial cell type. Recent studies concerning biliary innate immunity indicate that cholangiocytes express a variety of pathogen-recognition receptors such as Toll-like receptors (TLRs) [9, 10]. Infectious agents have been implicated in the

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