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Cited by 375

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Neutrophil Extracellular Trap Formation Is Associated with IL-1β and Autophagy-Related Signaling in Gout

Open access
Mitroulis, Ioannis, Kambas, Konstantinos, Chrysanthopoulou, Akrivi, Skendros, Panagiotis, Apostolidou, Eirini, Kourtzelis, Ioannis, Drosos, Georgios I., Boumpas, Dimitrios T., Ritis, Konstantinos·2011·PLoS ONE

Abstract

BACKGROUND: Gout is a prevalent inflammatory arthritis affecting 1-2% of adults characterized by activation of innate immune cells by monosodium urate (MSU) crystals resulting in the secretion of interleukin-1β (IL-1β). Since neutrophils play a major role in gout we sought to determine whether their activation may involve the formation of proinflammatory neutrophil extracellular traps (NETs) in relation to autophagy and IL-1β. METHODOLOGY/PRINCIPAL FINDINGS: Synovial fluid neutrophils from six patients with gout crisis and peripheral blood neutrophils from six patients with acute gout and six control subjects were isolated. MSU crystals, as well as synovial fluid or serum obtained from patients with acute gout, were used for the treatment of control neutrophils. NET formation was assessed using immunofluorescence microscopy. MSU crystals or synovial fluid or serum from patients induced NET formation in control neutrophils. Importantly, NET production was observed in neutrophils isolated from synovial fluid or peripheral blood from patients with acute gout. NETs contained the alarmin high mobility group box 1 (HMGB1) supporting their pro-inflammatory potential. Inhibition of phosphatidylinositol 3-kinase signaling or phagolysosomal fusion prevented NET formation, implicating autophagy in this process. NET formation was driven at least in part by IL-1β as demonstrated by experiments involving IL-1β and its inhibitor anakinra. CONCLUSIONS/SIGNIFICANCE: These findings document for the first time that activation of neutrophils in gout is associated with the formation of proinflammatory NETs and links this process to both autophagy and IL-1β. Modulation of the autophagic machinery may represent an additional therapeutic study in crystalline arthritides.

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Metadata

Authors
Mitroulis, I., Kambas, K., Chrysanthopoulou, A., Skendros, P., Apostolidou, E., Kourtzelis, I., Drosos, G. I., Boumpas, D. T., & Ritis, K.
Venue
PLoS ONE
Published
2011-12-16
Volume
6
Issue
12
Pages
e29318
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2095917499
Cited by
375
References
9
FWCI
6.87
Type
journal article
Language
en
Open access
gold

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Mitroulis, I., Kambas, K., Chrysanthopoulou, A., Skendros, P., Apostolidou, E., Kourtzelis, I., Drosos, G. I., Boumpas, D. T., & Ritis, K. (2011). Neutrophil Extracellular Trap Formation Is Associated with IL-1β and Autophagy-Related Signaling in Gout. PLoS ONE. https://doi.org/10.1371/journal.pone.0029318

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