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Toll‐like receptor 3 signaling attenuates liver regeneration
Author(s) -
ZordeKhvalevsky Elina,
Abramovitch Rinat,
Barash Hila,
SpivakPohis Irit,
Rivkin Ludmila,
Rachmilewitz Jacob,
Galun Eithan,
Giladi Hilla
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22973
Subject(s) - regeneration (biology) , liver regeneration , toll like receptor , receptor , toll , microbiology and biotechnology , signal transduction , medicine , biology , immunology , innate immune system
The current model for liver regeneration suggests that cell damage triggers Toll‐like receptor (TLR) signaling via MyD88, leading to the induction of nuclear factor κB (NF‐κB) and secretion of inflammatory cytokines that in turn prime liver regeneration. TLR3 is unique among TLRs in that it signals through TRIF (TIR domain‐containing adaptor‐inducing interferon‐β), not through MyD88, and may lead to activation of either the inflammatory or apoptotic pathway. The inflammatory pathway leads to NF‐κB activation, whereas the apoptotic pathway, believed to be mediated by Rip3, leads to caspase‐8 activation. In this study, we explored the role of TLR3 in liver regeneration by comparing the response to 70% partial hepatectomy of TLR3 wt and TLR3 −/− mice. We found that following partial hepatectomy, TLR3 −/− mice demonstrated earlier hepatocyte proliferation. Furthermore, within the first hours, we observed a dramatic TLR3‐dependent NF‐κB activation and an increase in Rip3 levels in hepatocytes, accompanied by caspase‐8 activation but without an apoptotic outcome. Conclusion: TLR3 plays an inhibitory role in the priming of liver regeneration, thus reinforcing the role of the innate immune system in balancing tissue regeneration. (H EPATOLOGY 2009.)