{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:04:50Z","timestamp":1791029090673,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,4,10]],"date-time":"2006-04-10T00:00:00Z","timestamp":1144627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2006,5]]},"abstract":"<jats:p><jats:bold>Abstract: Background: <\/jats:bold> Human intrahepatic biliary epithelial cells (HIBECs) may play active roles in both the innate and adaptive immune responses. Little is known, however, about the role of toll\u2010like receptors (TLRs) on HIBECs in inflammatory cholangiopathies.<\/jats:p><jats:p><jats:bold>Methods: <\/jats:bold> The expression of TLR1\u20139 and the biological responses to their ligands, lipopolysaccharide (LPS) or lipoteichoic acid (LTA), were studied in cultured HIBECs by reverse transcription\u2010polymerase chain reaction, immunoblotting, and enzyme\u2010linked immunosorbent assay.<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> HIBECs constitutively expressed transcripts encoding TLR1\u20136 and 9, as well as myeloid differentiation factor 88 (MyD88), MD2, and CD14. Stimulation of HIBECs with LPS resulted in translocation of NF\u2010\u03baB subunits from the cytoplasmic to the nuclear fraction, followed by increased secretion of a variety of chemokines\/cytokines, including interleukin\u20108 (IL\u20108), monocyte chemotactic protein\u20101 (MCP\u20101), and IL\u20106. Treatment with BAY11\u20107082 efficiently inhibited the LPS\u2010induced transcription and secretion of these chemokines\/cytokines. In HIBECs, the mitogen\u2010activated protein kinases (MAPKs) were also activated by LPS stimulation. These results indicated that LPS activates HIBECs via a TLR4\u2010MyD88\u2010dependent pathway. Stimulation of HIBECs with LTA induced the secretion of a similar profile of cytokines\/chemokines via a TLR2\u2010MyD88\u2010dependent pathway.<\/jats:p><jats:p><jats:bold>Conclusions: <\/jats:bold> In HIBECs, at least TLR2 and 4 are capable of mediating innate immune system function <jats:italic>in vitro<\/jats:italic>. This result, in conjunction with our recent finding that TLR4 expression is increased in biliary epithelial cells in primary biliary cirrhosis, suggests the involvement of TLRs in the development of chronic inflammatory cholangiopathies.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2006.01254.x","type":"journal-article","created":{"date-parts":[[2006,4,12]],"date-time":"2006-04-12T16:29:24Z","timestamp":1144859364000},"page":"467-476","source":"Crossref","is-referenced-by-count":127,"title":["Human intrahepatic biliary epithelial cells function in innate immunity by producing IL\u20106 and IL\u20108 via the TLR4\u2010NF\u2010\u03baB and \u2010MAPK signaling 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