EPS8 regulates an NLRP3 inflammasome-independent caspase-1 activation pathway in monosodium urate crystal-treated RAW264.7 macrophages

Jen Pin Chuang, Chuan Yu Kao, Jenq Chang Lee, Pin Ling, Ming Chei Maa, Tzeng Horng Leu

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Gout is an inflammatory arthritis caused by the phagocytosis of monosodium urate (MSU) crystal deposition in joints. NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome-dependent caspase-1 activation is implicated in the processing of interleukin-1β (IL-1β), which is the major effector cytokine in the acute inflammatory response of gout. Mechanisms underlying caspase-1 activation remain unclear. Epidermal growth factor receptor pathway substrate no. 8 (Eps8) is a signal transducer and actin filament organizer that plays a key role in lipopolysaccharide-stimulated phagocytosis in macrophages. Here, RAW264.7 macrophages that have no intact NLRP3 inflammasomes were used to investigate the role of Eps8 in MSU crystal-mediated caspase-1 activation. A kinetic study revealed that the induction of Eps8 expression by MSU crystals occurred before NLRP3, p46/p33 caspase-1, and mature IL-1β in RAW 264.7 cells. In addition, actin cytoskeleton dynamics was required for Eps8 induction and caspase-1 activation in MSU crystal stimulation. Silencing Eps8 had no effect on the basal expression of p46/p33 caspase-1 and NLRP3, but nearly abolished MSU crystal-induced NLRP3 expression and caspase-1 activation. Furthermore, MSU crystals induced Eps8–pro-caspase-1 complex formation and Eps8 formed a stable complex with p33 caspase-1, but not with NLRP3. In summary, our results demonstrated for the first time the importance of Eps8 in MSU crystal-mediated caspase-1 activation without the involvement of NLRP3 inflammasomes.

原文English
頁(從 - 到)487-493
頁數7
期刊Biochemical and Biophysical Research Communications
530
發行號3
DOIs
出版狀態Published - 2020 九月 24

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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