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Toll-like receptor 7 agonist induces hypoplasia of the biliary system in a neonatal mouse model
- Source :
- Journal of Microbiology, Immunology and Infection, Vol 51, Iss 2, Pp 166-173 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- Background/Purpose: Viral infections and innate immunity signaling, especially Toll-like receptor 7 (TLR7) have been implicated in the pathogenesis of biliary atresia (BA). Administration of rhesus rotavirus-type A to newborn Balb/c mice produces inflammatory obstruction of bile ducts, which resembles human BA. However, whether activation of TLR7 signaling plays a role in neonatal hepatobiliary injury remains to be investigated. Methods: TLR7 agonist, imiquimod (R837), was intraperitoneally administered to Balb/c mice within 24 hours of birth and then every other day. Morphological and histological injuries of liver and gallbladder were examined at 2 weeks. Hepatic messenger RNA expression of TLR7 signaling was studied. Terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick end labeling staining was used to delineate hepatobiliary apoptosis upon TLR7 stimulation. Results: TLR7 agonist, imiquimod, induced hypoplasia of the biliary system of neonatal Balb/c mice both in atrophic gallbladder and in paucity of intrahepatic bile ducts. There was significantly higher hepatic expression of TLR7 and downstream innate immunity-mediated interferon regulatory factor 7, interferon-α, and tumor necrosis factor-α. In addition, terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick end labeling-positive cells in the liver were increased after injections of TLR7 agonist. Conclusion: The results demonstrate that TLR7 activation may trigger innate immunity pathways and induce apoptosis and hypoplasia of neonatal biliary trees in Balb/c mice. The novel findings give an implication of pathogenesis of infantile cholestasis, such as BA. Keywords: animal model, Balb/c mice, biliary atresia, infantile cholestasis, innate immunity, toll-like receptor 7
- Subjects :
- Microbiology
QR1-502
Subjects
Details
- Language :
- English
- ISSN :
- 16841182
- Volume :
- 51
- Issue :
- 2
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Microbiology, Immunology and Infection
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.99bb61230a1c4b2785ccb44869338cff
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.jmii.2016.07.002