Toll-like receptor 3 signaling attenuates liver regeneration

Elina Zorde-Khvalevsky, Rinat Abramovitch, Hila Barash, Irit Spivak-Pohis, Ludmila Rivkin, Jacob Rachmilewitz, Eithan Galun*, Hilla Giladi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageAmerican English
Pages (from-to)198-206
Number of pages9
Issue number1
StatePublished - 2009
Externally publishedYes


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