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

Jun 30, 2020Biochemical and biophysical research communications

EPS8 controls a caspase-1 activation pathway unrelated to NLRP3 inflammasome in immune cells treated with urate crystals

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Abstract

Epidermal growth factor receptor pathway substrate no. 8 (Eps8) is essential for MSU crystal-mediated caspase-1 activation in macrophages lacking NLRP3 inflammasomes.

  • Eps8 expression is induced by MSU crystals before the activation of NLRP3 and caspase-1.
  • The dynamics of the actin cytoskeleton are necessary for the induction of Eps8 and subsequent caspase-1 activation.
  • Silencing Eps8 significantly reduces NLRP3 expression and caspase-1 activation triggered by MSU crystals.
  • MSU crystals lead to the formation of a complex between Eps8 and pro-caspase-1, indicating a direct role in the activation process.
  • Eps8 does not interact with NLRP3 but forms a stable complex with p33 caspase-1.

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