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

Area of Science:

• Environmental Health
• Rheumatology
• Toxicology

Background:

• Microplastics (MPs) are emerging environmental pollutants with potential human health risks.
• Systemic lupus erythematosus (SLE) is an autoimmune disease often involving joint inflammation.
• The impact of MPs on lupus arthritis remains under-researched.

Purpose of the Study:

• To investigate the effects of microplastic exposure on joint inflammation in a mouse model of SLE.
• To elucidate the mechanisms by which MPs might exacerbate lupus arthritis.

Main Methods:

• Oral administration of MPs (0.5 mg/kg or 5 mg/kg) to 8-week-old female MRL/lpr mice, a model for human SLE.
• Assessment of knee joint morphology, function, oxidative stress, apoptosis, fibrosis, and inflammatory cytokine secretion.
• Analysis of pyroptosis-related gene expression (NLRP3, CASPASE-1, GSDMD, IL-1β, IL-18) and signaling pathways (NF-κB, NRF2/KEAP1).

Main Results:

• MPs exposure induced synovial damage, affecting knee joint morphology and function.
• Increased oxidative stress, apoptosis, synovial fibrosis, and inflammatory cytokine secretion were observed.
• MPs significantly enhanced synovial cell pyroptosis by upregulating key inflammatory markers and activating NF-κB and NRF2/KEAP1 pathways.

Conclusions:

• In vivo findings suggest MPs exposure promotes synovial cell pyroptosis via oxidative stress and NF-κB signaling.
• MPs disrupt synovial tissue structure and function, potentially exacerbating joint damage in SLE.
• This study provides novel insights into the mechanisms of microplastic-induced synovial damage in the context of autoimmune joint disease.