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Induction of innate immune response and absence of subsequent tolerance to dsRNA in biliary epithelial cells relate to the pathogenesis of biliary atresia.
- Source :
-
Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2008 May; Vol. 28 (5), pp. 614-21. - Publication Year :
- 2008
-
Abstract
- Background/aims: Biliary epithelial cells (BECs) possess negative regulatory mechanisms of Toll-like receptor (TLR)-based tolerance to bacteria (e.g. endotoxin tolerance). Viral infections of the Reoviridae genus with a dsRNA genome are suspected to be part of the aetiology of biliary atresia (BA), but the negative biliary mechanisms remain unexplored.<br />Methods: Cultured human intrahepatic BECs (HIBECs) pretreated with polyinosinic-polycytidylic acid [poly(I:C)] (a synthetic analogue of viral dsRNA) for 24 h were exposed to poly(I:C) in fresh medium. The activation of nuclear factor-kappaB (NF-kappaB) and the expression of myxovirus resistance protein A (MxA) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNAs were evaluated. Moreover, after the pretreatment, the transition of these molecules was examined in poly(I:C)-free conditions.<br />Results: Treatment with poly(I:C) significantly upregulated NF-kappaB activity in fresh HIBECs, and pretreatment failed to show tolerance to poly(I:C). The production of MxA and TRAIL was also preserved. Moreover, upregulation in the pretreated HIBECs was well preserved in poly(I:C)-free medium for at least 72 h.<br />Conclusions: BECs fail to show tolerance to poly(I:C), and once innate immunity is activated it is sustained in poly(I:C)-free conditions, suggesting that the initiation of the immune response to dsRNA in HIBECs and its presence after the clearance of virus are closely associated with the progression of BA.
- Subjects :
- Bile Ducts, Intrahepatic cytology
Biliary Atresia virology
Cell Line
Epithelial Cells immunology
GTP-Binding Proteins metabolism
Humans
Immunity, Innate
Myxovirus Resistance Proteins
Poly I-C
TNF-Related Apoptosis-Inducing Ligand metabolism
Bile Ducts, Intrahepatic immunology
Biliary Atresia immunology
Immune Tolerance
RNA, Double-Stranded immunology
RNA, Viral immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1478-3231
- Volume :
- 28
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Liver international : official journal of the International Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 18433391
- Full Text :
- https://doi.org/10.1111/j.1478-3231.2008.01740.x