HMGB1 as an extracellular pro-inflammatory cytokine: Implications for drug-induced organic damage

Drug-induced organic damage encompasses various intricate mechanisms, wherein HMGB1, a non-histone chromosome-binding protein, assumes a significant role as a pivotal hub gene. The regulatory functions of HMGB1 within the nucleus and extracellular milieu are interlinked. HMGB1 exerts a crucial regulatory influence on key biological processes including cell survival, inflammatory regulation, and immune response. HMGB1 can be released extracellularly from the cell during these processes, where it functions as a pro-inflammation cytokine. HMGB1 interacts with multiple cell membrane receptors, primarily Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE), to stimulate immune cells and trigger inflammatory response. The excessive or uncontrolled HMGB1 release leads to heightened inflammatory responses and cellular demise, instigating inflammatory damage or exacerbating inflammation and cellular demise in different diseases. Therefore, a thorough review on the significance of HMGB1 in drug-induced organic damage is highly important for the advancement of pharmaceuticals, ensuring their effectiveness and safety in treating inflammation as well as immune-related diseases. In this review, we initially outline the characteristics and functions of HMGB1, emphasizing their relevance in disease pathology. Then, we comprehensively summarize the prospect of HMGB1 as a promising therapeutic target for treating drug-induced toxicity. Lastly, we discuss major challenges and propose potential avenues for advancing the development of HMGB1-based therapeutics.