Medicine and Health Sciences Commons^™

Caspase-11 Mediates Neutrophil Chemotaxis And Extracellular Trap Formation During Acute Gouty Arthritis Through Alteration Of Cofilin Phosphorylation, Kyle Caution, Nicholas Young, Frank Robledo-Avila, Kathrin Krause, Arwa Abu Khweek, Kaitlin Hamilton, Asmaa Badr, Anup Vaidya, Kylene Daily, Hawin Gosu, Midhun N. K. Anne, Mostafa Eltobgy, Duaa Dakhlallah, Sudha Argwal, Shady Estfanous, Xiaoli Zhang, Santiago Partida-Sanchez, Mikhail A. Gavrilin, Wael N. Jarjour, Amal O. Amer

Faculty & Staff Scholarship

Gout is characterized by attacks of arthritis with hyperuricemia and monosodium urate (MSU) crystal-induced inflammation within joints. Innate immune responses are the primary drivers for tissue destruction and inflammation in gout. MSU crystals engage the Nlrp3 inflammasome, leading to the activation of caspase-1 and production of IL-1β and IL-18 within gout-affected joints, promoting the influx of neutrophils and monocytes. Here, we show that caspase-11−/− mice and their derived macrophages produce significantly reduced levels of gout-specific cytokines including IL-1β, TNFα, IL-6, and KC, while others like IFNγ and IL-12p70 are not altered. IL-1β induces the expression of caspase-11 in an IL-1 …