biostudies-literatureUnknown21(6)Liu QHyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1β expression levels and interleukin-1β (IL-1β) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor^-/- mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in GCellular & molecular immunology561-574https://www.ebi.ac.uk/biostudies/studies/S-EPMC11143353biostudies-literatureGSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14.PMC11143353Jiao LZou WYYang LXLiu QMa ZYu JSu LYChen CYe MSYao YGfalseGSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14.Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1β expression levels and interleukin-1β (IL-1β) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor^-/- mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in G2024-01-01T00:00:00Z2024 Jun2026-06-01T11:47:48.324Z2026-04-08T11:55:31.695ZS-EPMC111433533857058810.1038/s41423-024-01155-9