To examine the pathogenic roles of HMGB1 and procathepsin-L in dysregulated inflammation and propose novel therapeutic interventions targeting the HMGB1-pCTS-L axis, emphasizing its significance in inflammatory disorders.
Key Findings:
HMGB1 directly upregulates pCTS-L expression and release, initiating a sustained inflammatory loop, which may complicate treatment strategies.
The HMGB1-pCTS-L axis predominantly activates the non-canonical NF-κB pathway, suggesting a targeted approach could mitigate chronic inflammation.
Tetranectin inhibits HMGB1 release but facilitates HMGB1-induced pyroptosis, indicating a complex role in inflammation.
The P2–1 peptide selectively targets extracellular HMGB1 at pathological sites, enhancing safety and precision in treatment, potentially improving patient outcomes.
Interpretation:
The HMGB1-pCTS-L axis represents a critical pathway in inflammatory diseases, with potential for targeted therapeutic interventions that avoid broad immunosuppression, offering a more refined treatment strategy.
Limitations:
The review primarily focuses on the HMGB1-pCTS-L axis without extensive exploration of other inflammatory pathways, such as those involving IL-1 or TNF.
Further clinical studies are needed to validate the efficacy and safety of the P2–1 peptide in human subjects, particularly in diverse populations.
Conclusion:
Targeting the HMGB1-pCTS-L axis offers a promising strategy for treating inflammatory disorders, with potential applications in sepsis and rheumatoid arthritis, and could significantly enhance treatment outcomes.
