Microplastics Exposure Aggravates Synovitis and Pyroptosis in SLE by Activating NF-κB and NRF2/KEAP1 Signaling

Microplastics (MPs) represent an emerging pollutant capable of entering the human body through the respiratory and digestive systems, thereby posing significant health risks. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organ systems, often presenting with polyarticular joint manifestations. Despite its relevance, there is currently limited research on the impact of MPs on lupus arthritis. This study aims to investigate the effects of MPs on joint inflammation in SLE. MRL/lpr mice exhibit SLE similar to that of humans. We administered either 0.5 mg/kg or 5 mg/kg of MPs to 8-week-old female MRL/lpr mice via oral ingestion. Our findings indicate that exposure to MPs can lead to synovial damage, adversely affecting the morphology and function of the knee joint, along with increased oxidative stress, apoptosis, synovial fibrosis, and the secretion of inflammatory cytokines. Notably, MPs significantly enhanced synovial cell pyroptosis by upregulating the expression of NLRP3, CASPASE-1, GSDMD, IL-1β, and IL-18. Mechanistic analyses further demonstrated that MPs exposure activates the NF-κB and NRF2/KEAP1 signaling pathways. Overall, our in vivo findings suggest that MPs exposure promotes synovial cell pyroptosis through increased oxidative stress and NF-κB signaling, thereby disrupting the structure and function of synovial tissue. This research provides new insights into the synovial damage associated with MPs exposure.