TBBPA facilitates splenic inflammation and pyroptosis by targeting HMGB1.

As a widely used brominated flame retardant, tetrabromobisphenol A (TBBPA) is heavily utilized and has led to major concerns about its environmental and health implications. Although TBBPA has been detected in various environmental and biological matrices globally, its impact on the spleen and the underlying mechanisms remain poorly understood. HMGB1 is a protein released during pyroptosis which can trigger inflammation by activating the TLR4/MyD88/NF-κB pathway, leading to the production of inflammatory cytokines and chemokines. Nonetheless, its impact of HMGB1 on spleen damage caused by TBBPA is still uncertain. This study aims to explore the effect of TBBPA on spleen injury in mice and elucidates the role of HMGB1 in this process. In this study, male ICR mice were treated with TBBPA (50 mg/(kg·day)) for 28 days. Results showed that TBBPA induced splenic injury, characterized by white pulp reduction, red pulp congestion, lymphatic hyperplasia, and inflammatory infiltration. Moreover, vacuolation was observed in the mitochondria of the TBBPA exposed group, with the majority of mitochondrial cristae either disrupted or had vanished. Mechanistically, TBBPA upregulates HMGB1, which activates the TLR4/MyD88/NF-κB pathway and subsequently promotes NLRP3-mediated pyroptosis, ultimately exacerbating the inflammatory response. Our findings indicate that HMGB1 could be an effective target for addressing inflammatory and immune disorders.