Supplementary Material for: Injury Resistance in the Setting of Liver Fibrosis Is Accompanied by the Inhibition of High-Mobility Group Box-1 Translocation and Release

Background: Injury resistance occurring in the setting
of liver fibrosis is an interesting phenomenon not yet well
characterized. In the present study, we investigated dynamically the
injury resistance against acute challenge using animal models of hepatic
fibrosis and spontaneous resolution, and focused on high-mobility group
box-1 (HMGB1), an important proinflammatory mediator. Methods: The hepatic damage of control, fibrosis (CCl4, 6 weeks), and regressive mice with or without CCl4
challenge was dynamically observed and compared. The translocation and
release of HMGB1 were assessed by immunohistochemical staining and
enzyme-linked immunosorbent assay, respectively. The gene expression of
proinflammatory mediators was detected by real-time PCR. Results: Our data showed that the fibrotic mice were invulnerable to acute CCl4
insult. The injury resistance diminished along with the resolution of
liver fibrosis. Acute insult triggered the translocation and release of
HMGB1 in control mice, which were remarkably inhibited in fibrotic mice,
even under acute challenge. Nevertheless, regressive mice exhibited
obvious translocation upon insult, especially for R12d mice.
HMGB1-related proinflammatory immune responses were suppressed in
fibrotic mice; however, they were restored in regressive mice upon
insult. Conclusion: The injury resistance in the setting
of liver fibrosis is accompanied by the inhibition of HMGB1
translocation and release as well as the suppression of HMGB1-related
proinflammatory immune responses.