N4-acetylcytidine is required for sustained NLRP3 inflammasome activation via HMGB1 pathway in microglia
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Updated: Jan 28, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
JuanJuan Duan1, Qifang Zhang2, Xiaohong Hu2
1Department of Neurology, the Third Affiliated Hospital of Guizhou Medical University, Duyun 558000, China; Department of Neurology, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
Abstract:
Persistent inflammasome activation contributes to chronic, low grade inflammation. However, it is unclear how the inflammasome activation is sustained after initiation. Here we reported that N4-acetylcytidine (N4A), a nucleoside metabolite, activated microglia and sustained NLRP3 inflammasome activation by inducing HMGB1 signaling. Released HMGB1 through N4A activated NFκB and induced NLRP3 expression. HMGB1 silencing abolished N4A-stimulated NFκB activation, NLRP3 and persistent HMGB1 expression. In addition, inhibiting NLRP3 expression by RNAi abrogated N4A-mediated HMGB1 expression. Lack of NLRP3 inflammasome adaptor named apoptosis-associated speck-like protein containing a CARD (ASC) abrogated N4A-induced HMGB1 expression, NFκB activation, and NLRP3 expression. Taken together, our results reveal a novel role of N4A in activation of NLRP3 inflamasome via HMGB1 feedback.
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