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タイトル: Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by upregulation of IRAK-M
著者: Harada, Kenichi link image link image
Isse, Kumiko
Sato, Yasunori link image link image
Ozaki, Satoru
Nakanuma, Yasuni link image
原田, 憲一
佐藤, 保則
尾﨑, 聡
中沼, 安二
発行日: 2006年10月
出版社(者): Blackwell Publishing
雑誌名: Liver International
ISSN: 1478-3223
巻: 26
号: 8
開始ページ: 935
終了ページ: 942
キーワード: Biliary epithelial cells
Endotoxin tolerance
Innate immunity
IRAK
Toll-like receptor
抄録: Background/Aim: Biliary epithelial cells possess an innate immune system consisting of Toll-like receptors (TLRs). Although the human bile contains lipopolysaccharide (LPS) in normal as well as diseased livers, LPS physiologically does not elicit an inflammatory response in the biliary tree. This absence of a response to LPS could be due to the 'endotoxin tolerance'speculated to maintain innate immune homeostasis in organs. Our aim here is to clarify the presence and molecular mechanisms of endotoxin tolerance of biliary epithelium. Methods and Results: In nuclear factor-κB (NF-κB)-DNA binding assays using three-cultured human intrahepatic biliary epithelial cell (HIBEC) lines, all the cells responded to LPS (TLR4 ligand) by activating NF-κB, but pretreatment with LPS for 24h effectively induced tolerance against any subsequent stimulation with LPS (endotoxin tolerance). This tolerance was also induced by pretreatment with Pam3Cys-Ser-(Lys)4 trihydrochloride (Pam3CKS4, TLR1/2 ligand). Then, real-time polymerase chain treaction and Western blotting revealed that LPS treatment upregulated the expression of IRAK-M (a negative regulator of TLR signaling), but did not affect interleukin-1 receptor-associated kinase-1 (IRAK-1, an essential molecule of TLR signaling), in HIBECs. Moreover, immunohistochemistry revealed that IRAK-M was diffusely expressed in intrahepatic bile ducts. Conclusions: This study showed that the mechanism of endotoxin tolerance exists in the intrahepatic biliary tree and is possibly induced by the expression of IRAK-M in the intrahepatic biliary epithelium, suggesting that the endotoxin tolerance is important in maintaining innate immune biliary homeostasis. © 2006 Blackwell Munksgaard.
DOI: 10.1111/j.1478-3231.2006.01325.x
URI: http://hdl.handle.net/2297/7543
資料種別: Journal Article
版表示: author
出現コレクション:1. 査読済論文(医学・保健)

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