{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:57:08Z","timestamp":1761919028081},"reference-count":40,"publisher":"Wiley","issue":"s3","license":[{"start":{"date-parts":[[2007,10,10]],"date-time":"2007-10-10T00:00:00Z","timestamp":1191974400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:p>The intrahepatic biliary tree is a conduit of bile which contains pathogen\u2010associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) originated from intestinal flora. Human biliary epithelial cells (BEC) express toll\u2010like receptors (TLR) and intracellular adaptor molecules and secrete antibiotic peptides and (pro)inflammatory cytokines via the activation of nuclear transcription factors. However, although human bile contains several PAMPs in normal as well as diseased livers, PAMPs physiologically do not elicit an inflammatory response in the biliary tree, suggesting that tolerance against commensal PAMPs including LPS (endotoxin tolerance) is important in maintaining the homeostasis of biliary innate immunity. Negative regulators of intracellular TLR signalings, peroxisome proliferator activating receptor\u2010\u03b3 (PPAR\u2010\u03b3) and IRAK\u2010M, are associated with the endotoxin tolerance in BEC. <jats:italic>In vivo<\/jats:italic>, PPAR\u2010\u03b3 and IRAK\u2010M are ubiquitously expressed in intrahepatic biliary epithelium, while the expression of PPAR\u2010\u03b3 is reduced in damaged bile ducts of primary biliary cirrhosis (PBC). In addition to antibiotic peptides, several cytokines andchemokines are also secreted from BEC as an innate immune response and these humoral components participate in attracting immunocytes and modulating peribiliary cytokine milieu. BEC have receptors for several cytokines and the expression of TLR in BEC is affected by cytokines, suggesting that biliary innate immunity is regulated by an acquired immunity. A T\u2010helper (Th)1\u2010type cytokine, interferon\u2010\u03b3, downregulates PPAR\u2010\u03b3 and upregulates TLR, and consequently increases the susceptibility of biliary innate immunity. Because periductal cytokine milieu in PBC is Th1\u2010dominant, the increased susceptibility to PAMPs may be associated with the development of cholangiopathy in PBC. Biliary innate immunity is speculated to be associated with the pathogenesis of biliary diseases as well as the defense against biliary microbial infection.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2007.00247.x","type":"journal-article","created":{"date-parts":[[2007,10,11]],"date-time":"2007-10-11T03:22:56Z","timestamp":1192072976000},"source":"Crossref","is-referenced-by-count":21,"title":["Biliary innate immunity and 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