IL1A regulates MSU-induced apoptosis and inflammatory response through TLR4/MyD88/NF-κB signaling pathway.

Background

The increased inflammation associated with interleukin-1α (IL-1A) induced by monosodium urate (MSU) crystal-induced gouty arthritis is mediated through the NLRP3 inflammasome and NF-κB signaling pathways. This study investigated the role of IL1A in MSU-mediated inflammation and its therapeutic potential.

Methods

MSU crystals were applied to THP-1 macrophages and human vascular endothelial cells (HUVECs) with or without IL1A knockdown. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting (WB), cell counting kit-8 (CCK-8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were used to assess IL1A expression, cell viability, apoptosis, and the generation of inflammatory cytokines. The activation of the NLRP3 inflammasome and TLR4/MyD88/NF-κB pathways was evaluated, with TAK-242 used to assess synergistic effects.

Results

MSU increased IL1A expression, induced apoptosis, and reduced cell viability in HUVECs, effects reversed by IL1A knockdown. IL1A knockdown media mitigated apoptosis in HUVECs exposed to conditioned media from MSU-stimulated THP-1 macrophages. IL1A knockdown reduced MSU-induced proinflammatory cytokines and NLRP3 activation in THP-1 cells. TAK-242 showed synergistic effects, while IL1A knockdown inhibited TLR4/MyD88/NF-κB activation.

Conclusions

IL1A promotes cell death and inflammation in MSU-induced gout. Knockdown of IL1A mitigates these effects, suggesting it may be a potential therapeutic target for MSU-induced inflammation.