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Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by upregulation of IRAK-M.
Liver Int. 2006 Oct; 26(8):935-42.LI

Abstract

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-kappaB (NF-kappaB)-DNA binding assays using three-cultured human intrahepatic biliary epithelial cell (HIBEC) lines, all the cells responded to LPS (TLR4 ligand) by activating NF-kappaB, but pretreatment with LPS for 24 h effectively induced tolerance against any subsequent stimulation with LPS (endotoxin tolerance). This tolerance was also induced by pretreatment with Pam(3)Cys-Ser-(Lys)(4) trihydrochloride (Pam(3)CKS(4), 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.

Authors+Show Affiliations

Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16953833

Citation

Harada, Kenichi, et al. "Endotoxin Tolerance in Human Intrahepatic Biliary Epithelial Cells Is Induced By Upregulation of IRAK-M." Liver International : Official Journal of the International Association for the Study of the Liver, vol. 26, no. 8, 2006, pp. 935-42.
Harada K, Isse K, Sato Y, et al. Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by upregulation of IRAK-M. Liver Int. 2006;26(8):935-42.
Harada, K., Isse, K., Sato, Y., Ozaki, S., & Nakanuma, Y. (2006). Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by upregulation of IRAK-M. Liver International : Official Journal of the International Association for the Study of the Liver, 26(8), 935-42.
Harada K, et al. Endotoxin Tolerance in Human Intrahepatic Biliary Epithelial Cells Is Induced By Upregulation of IRAK-M. Liver Int. 2006;26(8):935-42. PubMed PMID: 16953833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by upregulation of IRAK-M. AU - Harada,Kenichi, AU - Isse,Kumiko, AU - Sato,Yasunori, AU - Ozaki,Satoru, AU - Nakanuma,Yasuni, PY - 2006/9/7/pubmed PY - 2007/2/28/medline PY - 2006/9/7/entrez SP - 935 EP - 42 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int VL - 26 IS - 8 N2 - 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-kappaB (NF-kappaB)-DNA binding assays using three-cultured human intrahepatic biliary epithelial cell (HIBEC) lines, all the cells responded to LPS (TLR4 ligand) by activating NF-kappaB, but pretreatment with LPS for 24 h effectively induced tolerance against any subsequent stimulation with LPS (endotoxin tolerance). This tolerance was also induced by pretreatment with Pam(3)Cys-Ser-(Lys)(4) trihydrochloride (Pam(3)CKS(4), 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. SN - 1478-3223 UR - https://www.unboundmedicine.com/medline/citation/16953833/Endotoxin_tolerance_in_human_intrahepatic_biliary_epithelial_cells_is_induced_by_upregulation_of_IRAK_M_ L2 - https://doi.org/10.1111/j.1478-3231.2006.01325.x DB - PRIME DP - Unbound Medicine ER -