Vaccination Against HMGB1 Protects Mice from CCl₄-Induced Liver Injury, Inflammation, and Fibrosis.
4 affiliations
- 1Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, China.
- 2Center of Reproductive Medicine, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
- 3Department of Rehabilitation Medicine, Shaanxi Provincial People's Hospital, Xi'an, China.
- 4Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi, 710061, China. [email protected].
Abstract
Extracellular high mobility group box 1 (HMGB1) serves as a key damage-associated molecular pattern that drives the pathological process of inflammatory liver injury; however, its role in liver fibrosis and the underlying mechanisms need to be elucidated. To investigate the proinflammatory and profibrotic roles of extracellular HMGB1, we used an adenovirus-mediated system to measure HMGB1 secretion in mice. We subsequently constructed two recombinant proteins, PfTrx-HMGB1¹⁷(95 - 111) and HBcΔ-HMGB1³⁴(150 - 183), targeting the interactions of HMGB1 with its receptors, namely, toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), respectively. Mice were immunized with the two recombinant proteins to assess neutralizing antibody induction and the protective effects of the HMGB1 vaccines against carbon tetrachloride (CCl₄)-induced liver fibrosis. Our results revealed the nucleocytoplasmic translocation of HMGB1 in the livers of both humans and mice with fibrosis. Extracellular HMGB1 induced liver inflammation and fibrogenesis in mice. Immunization with the two HMGB1 vaccines resulted in the production of high levels of anti-HMGB1 neutralizing antibodies, which inhibited the activation of hepatic stellate cells (LX-2) and the production of proinflammatory and profibrotic factors in RAW 264.7 cells. Furthermore, vaccination with these compounds significantly protected against CCl₄-induced liver injury, inflammation, and fibrosis in mice. These findings demonstrate that extracellular HMGB1, by binding to TLR4 or RAGE, is pivotal in driving liver inflammation and fibrosis. Vaccination against HMGB1 through disruption of interaction with TLR4 or RAGE represents a promising therapeutic strategy for hepatic fibrosis.
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BibTeX
@article{li2026vaccination,
title = {{Vaccination Against HMGB1 Protects Mice from CCl₄-Induced Liver Injury, Inflammation, and Fibrosis.}},
author = {Qian Li and Hanchao Li and Yongwei Huo and Hong Tian and Li Zhu and Xiaoyan Zheng and Wengang Sun and Xueting Zhang and Zhiming Hao},
journal = {Inflammation},
year = {2026},
month = aug,
doi = {10.1007/s10753-026-02578-4},
url = {https://europepmc.org/article/MED/42955153},
note = {CC BY},
}
RIS
TY - JOUR
TI - Vaccination Against HMGB1 Protects Mice from CCl₄-Induced Liver Injury, Inflammation, and Fibrosis.
AU - Qian Li
AU - Hanchao Li
AU - Yongwei Huo
AU - Hong Tian
AU - Li Zhu
AU - Xiaoyan Zheng
AU - Wengang Sun
AU - Xueting Zhang
AU - Zhiming Hao
PY - 2026
DA - 2026/08/01
JO - Inflammation
DO - 10.1007/s10753-026-02578-4
UR - https://europepmc.org/article/MED/42955153
AB - Extracellular high mobility group box 1 (HMGB1) serves as a key damage-associated molecular pattern that drives the pathological process of inflammatory liver injury; however, its role in liver fibrosis and the underlying mechanisms need to be elucidated. To investigate the proinflammatory and profibrotic roles of extracellular HMGB1, we used an adenovirus-mediated system to measure HMGB1 secretion in mice. We subsequently constructed two recombinant proteins, PfTrx-HMGB1¹⁷(95 - 111) and HBcΔ-HMGB1³⁴(150 - 183), targeting the interactions of HMGB1 with its receptors, namely, toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), respectively. Mice were immunized with the two recombinant proteins to assess neutralizing antibody induction and the protective effects of the HMGB1 vaccines against carbon tetrachloride (CCl₄)-induced liver fibrosis. Our results revealed the nucleocytoplasmic translocation of HMGB1 in the livers of both humans and mice with fibrosis. Extracellular HMGB1 induced liver inflammation and fibrogenesis in mice. Immunization with the two HMGB1 vaccines resulted in the production of high levels of anti-HMGB1 neutralizing antibodies, which inhibited the activation of hepatic stellate cells (LX-2) and the production of proinflammatory and profibrotic factors in RAW 264.7 cells. Furthermore, vaccination with these compounds significantly protected against CCl₄-induced liver injury, inflammation, and fibrosis in mice. These findings demonstrate that extracellular HMGB1, by binding to TLR4 or RAGE, is pivotal in driving liver inflammation and fibrosis. Vaccination against HMGB1 through disruption of interaction with TLR4 or RAGE represents a promising therapeutic strategy for hepatic fibrosis.
SN - 0360-3997
SN - 1573-2576
ER -