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.