Related Experiment Video
Updated: Mar 29, 2026
Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice
Published on: March 10, 2017
HMGB1 induced inflammatory effect is blocked by CRISPLD2 via MiR155 in hepatic fibrogenesis
Haoye Zhang1, Zhenguo Liu1, Shikun Liu2
1Department of Infectious Disease, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Abstract:
A number of studies have showed that High mobility group box-1 (HMGB1), which played key role in inflammation activation by triggering the toll like receptor 4 (TLR4) signaling axis in hepatic fibrogenesis, may share similar inflammation stimulating mechanism with LPS. Herein, we introduced a recently established anti-LPS protein cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) to investigate endogenous protection mechanism of HMGB1 induced inflammatory response. Our results shows that stromal cells and monocytes showed an evaluated pattern for CRISPLD2 expression after HMGB1 treatment, which was dependent on the integrity of TLR4 function. Pro-inflammatory Cytokines levels were significantly elevated after CRISPLD2 silencing despite the HMGB1 status. Soluble CRISPLD2 administration relieve the HMGB1 dependent pro-inflammatory cytokines release. Interestingly, we found that miRNA 155 play a key role in the process. Our data suggest that CRISPLD2 may have a unique anti-HMGB1 effect via miRNA and play an important role in immune balance.
Insights
High mobility group box-1 (HMGB1) triggers inflammation via toll-like receptor 4 (TLR4). Cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) demonstrates an anti-HMGB1 effect, potentially restoring immune balance.
Area of Science:
- Immunology
- Molecular Biology
- Hepatology
Background:
- High mobility group box-1 (HMGB1) is implicated in hepatic fibrogenesis through toll-like receptor 4 (TLR4) signaling.
- Lipopolysaccharide (LPS) and HMGB1 may share similar inflammatory activation pathways.
- Cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) is a recently identified anti-LPS protein.
Purpose of the Study:
- To investigate the endogenous protective mechanism of cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) against High mobility group box-1 (HMGB1) induced inflammation.
- To explore the role of toll-like receptor 4 (TLR4) in CRISPLD2 expression and function.
- To elucidate the involvement of miRNA 155 in the anti-inflammatory effects of CRISPLD2.
Main Methods:
- HMGB1 treatment of stromal cells and monocytes.
- CRISPLD2 gene silencing and soluble CRISPLD2 administration.
- Measurement of pro-inflammatory cytokines levels.
- Analysis of toll-like receptor 4 (TLR4) function integrity.
- Investigation of miRNA 155 activity.
Main Results:
- HMGB1 treatment upregulated CRISPLD2 expression in stromal cells and monocytes, dependent on TLR4.
- CRISPLD2 silencing exacerbated HMGB1-induced pro-inflammatory cytokine release.
- Soluble CRISPLD2 administration mitigated HMGB1-driven cytokine production.
- MicroRNA 155 was identified as a key mediator in the CRISPLD2-HMGB1 interaction.
Conclusions:
- CRISPLD2 exhibits a unique anti-HMGB1 effect, potentially mediated by miRNA 155.
- CRISPLD2 plays a significant role in maintaining immune homeostasis.
- The findings suggest CRISPLD2 as a potential therapeutic target for HMGB1-related inflammatory conditions.
