Caspase-11 Mediates Neutrophil Chemotaxis and Extracellular Trap Formation During Acute Gouty Arthritis Through Alteration of Cofilin Phosphorylation.

Autor:	Caution K; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Young N; Department of Rheumatology and Immunology, The Ohio State University Medical Center, Columbus, OH, United States., Robledo-Avila F; Center for Microbial Pathogenesis, Nationwide Children's Hospital, Columbus, OH, United States., Krause K; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Abu Khweek A; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States.; Department of Biology and Biochemistry, Birzeit University, West Bank, Palestine., Hamilton K; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Badr A; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Vaidya A; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Daily K; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Gosu H; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Anne MNK; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Eltobgy M; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Dakhlallah D; Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, United States., Argwal S; Department of Rheumatology and Immunology, The Ohio State University Medical Center, Columbus, OH, United States., Estfanous S; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States., Zhang X; Center for Biostatistics, The Ohio State University Medical Center, Columbus, OH, United States., Partida-Sanchez S; Center for Microbial Pathogenesis, Nationwide Children's Hospital, Columbus, OH, United States., Gavrilin MA; Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH, United States., Jarjour WN; Department of Rheumatology and Immunology, The Ohio State University Medical Center, Columbus, OH, United States., Amer AO; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2019 Nov 15; Vol. 10, pp. 2519. Date of Electronic Publication: 2019 Nov 15 (Print Publication: 2019).
DOI:	10.3389/fimmu.2019.02519
Abstrakt:	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 receptor-dependent manner in macrophages contributing to the priming of macrophages during sterile inflammation. The absence of caspase-11 reduced the ability of macrophages and neutrophils to migrate in response to exogenously injected KC in vivo . Notably, in vitro, caspase-11 -/- neutrophils displayed random migration in response to a KC gradient when compared to their WT counterparts. This phenotype was associated with altered cofilin phosphorylation. Unlike their wild-type counterparts, caspase-11 -/- neutrophils also failed to produce neutrophil extracellular traps (NETs) when treated with MSU. Together, this is the first report demonstrating that caspase-11 promotes neutrophil directional trafficking and function in an acute model of gout. Caspase-11 also governs the production of inflammasome-dependent and -independent cytokines from macrophages. Our results offer new, previously unrecognized functions for caspase-11 in macrophages and neutrophils that may apply to other neutrophil-mediated disease conditions besides gout. (Copyright © 2019 Caution, Young, Robledo-Avila, Krause, Abu Khweek, Hamilton, Badr, Vaidya, Daily, Gosu, Anne, Eltobgy, Dakhlallah, Argwal, Estfanous, Zhang, Partida-Sanchez, Gavrilin, Jarjour and Amer.)
Databáze:	MEDLINE
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